form-1environmentclearance.nic.in/writereaddata/online/tor/02...2 appendix i (see paragraph - 6)...

1

FORM-1

for

PROPOSED EXPANSION (FROM 25 TO 200

MT/MONTH) OF API & API INTERMEDITES IN

EXISTING UNIT

of

M/s. ALEMBIC PHARMACUETICALS LIMITED

(API UNIT-II)

SURVEY NO.: 137, 138, 139, 140, 144P & 145P,

AT: PANELAV, POST: TAJPURA, TAL: HALOL,

DIST: - PANCHMAHAL-389 350 (GUJ)

Prepared by:

NABL Accredited Testing Laboratory

ISO 9001:2008 Certified Company

Aqua-Air Environmental Engineers P. Ltd.

403, Centre Point, Nr. Kadiwala School, Ring

Road, Surat - 395002

NABL Accredited Testing Laboratory

ISO 9001:2008 Certified Company

Aqua-Air Environmental Engineers P. Ltd.

403, Centre Point, Nr. Kadiwala School, Ring

Road, Surat - 395002

2

APPENDIX I

(See paragraph - 6)

FORM 1

(I) Basic Information

Sr.

No.

Item Details

1. Name of the project/s Alembic Pharmaceuticals Limited (API Unit-II)

2. S. No. in the schedule 5(f)

3. Proposed capacity/area/length/tonnage

to be handled/command area/lease

area/number of wells to be drilled

For detail Please refer Annexure – I

4. New/Expansion/Modernization Expansion

5. Existing Capacity/Area etc. --

6. Category of Project i.e. ‘A’ or ‘B’ ‘A’

7. Does it attract the general condition? If

yes, please specify.

No

8. Does it attract the specific condition? If

yes, please specify.

No

9. Location

Plot/Survey/Khasra No. Survey No.137, 138, 139, 140, 144P & 145P.

Village Panelav

Tehsil Halol

District Panchmahal

State Gujarat

10. Nearest railway station/airport along with

distance in kms. Vadodara – 45 Km

11. Nearest Town, city, District Headquarters

along with distance in kms. Halol - 10 km

12. Village Panchayats, Zilla Parishad,

Municipal Corporation, local body

(complete postal address with telephone

nos. to be given)

Not applicable

13. Name of the applicant M/s. Alembic Pharmaceuticals Limited (API Unit-II)

14. Registered Address M/s. Alembic Pharmaceuticals Limited (API Unit-II)

Survey No.: 137, 138, 139, 140, 144P & 145P,

At: Panelav, Post: Tajpura, Tal: Halol,

Dist.: Panchmahal-389 350, Gujarat

15. Address for correspondence: M/s. Alembic Pharmaceuticals Limited (API Unit-II)

Survey No.: 137, 138, 139, 140, 144P & 145P,


Dist.: Panchmahal-389 350, Gujarat

Name Mr. R. S. Joshi

Designation (Owner/Partner/CEO) AGM (Environment)

Address M/s. Alembic Pharmaceuticals Limited (API Unit-II)

Survey No.: 137, 138, 139, 140, 144P & 145P,


Dist: Panchmahal-389 350, Gujarat

Pin Code 389 350

E-mail [email protected]

3

[email protected]

Telephone No. (02676) 664301

(0265) 3007321

+91 9825321699

Fax No. (02676) 247255

16. Details of Alternative Sites examined, if

any.

Location of these sites should be shown

on a topo sheet.

NA

17. Interlinked Projects NA

18. Whether separate application of

interlinked project has been submitted?

NA

19. If yes, date of submission NA

20. If no, reason NA

21. Whether the proposal involves

approval/clearance under: if yes, details

of the same and their status to be given.

(a) The Forest (Conservation) Act, 1980?

(b) The Wildlife (Protection) Act, 1972?

(c) The C.R.Z. Notification, 1991?

No

22. Whether there is any Government

Order/Policy relevant/relating to the site?

No

23. Forest land involved (hectares) NA

24. Whether there is any litigation pending

against the project and/or land in which

the project is propose to be set up?

(a) Name of the Court

(b) Case No.

(c) Orders/directions of the Court, if any

and its relevance with the proposed

project.

NA

Capacity corresponding to sectoral activity (such as production capacity for

manufacturing, mining lease area and production capacity for mineral production, area for mineral exploration, length for linear transport infrastructure, generation capacity for power generation etc.,)

(II) Activity

1. Construction, operation or decommissioning of the Project involving actions, which will cause

physical changes in the locality (topography, land use, changes in water bodies, etc.)

Sr.

No.

Information/Checklist confirmation Yes/

No

Details there of with approximate

quantities fraters, wherever possible)

with source of information data

1.1 Permanent or temporary change in land

use, land cover or topography including

increase intensity of land use (with respect

to local land use plan)

No Proposed Expansion within existing unit

with addition of 3 new Plots.

Existing Plot Area – 37,332 m2

Additional Plot Area – 41,220 m2

Total Plot Area – 78,552 m2

4

Existing Green Belt Area – 20,194 m2

Additional Green Belt Area – 5,817 m2

Total Green Belt Area – 26,011 m2

1.2 Clearance of existing land, vegetation and

Buildings?

Yes Minor site clearance activities shall be

carried out to clear shrubs and weed.

1.3 Creation of new land uses?

No The project site is located on level

ground, which does not require any

major land filling for area grading work.

1.4 Pre-construction investigations e.g. bore

Houses, soil testing?

No

1.5 Construction works? Yes For detail Please refer Annexure – II

1.6 Demolition works? No There will not be Demolition work at the

site.

1.7 Temporary sites used for construction

works or housing of construction workers?

Yes

1.8 Above ground buildings, structures or

earthworks including linear structures, cut

and fill or excavations

Yes For detail Please refer Annexure – II

1.9 Underground works mining or tunneling? No

1.10 Reclamation works? No

1.11 Dredging? No

1.12 Off shore structures? No

1.13 Production and manufacturing processes? Yes For detail Please refer Annexure -III

1.14 Facilities for storage of goods or materials?

Yes Areas for storage tank farm, raw

materials and finished products will be

developed for the proposed Expansion

project.

1.15 Facilities for treatment or disposal of solid

waste or liquid effluents?

Yes For detail please refer Annexure –V &

VI.

1.16 Facilities for long term housing of

operational workers?

No

1.17 New road, rail or sea traffic during

Construction or Operation?

No

1.18 New road, rail, air waterborne or other

transport infrastructure including new or

altered routes and stations, ports, airports

etc?

No

1.19 Closure or diversion of existing transport

routes or infrastructure leading to changes

in traffic movements?

No

1.20 New or diverted transmission lines or

Pipelines?

No There will not be said work at the site.

1.21 Impoundment, damming, culverting,

realignment or other changes to the

hydrology of watercourses or aquifers?

No

1.22 Stream crossings? No

1.23 Abstraction or transfers of water form

ground or surface waters?

Yes Water requirement will be met through

Ground Water (Existing) & Narmada

Water (Proposed).

1.24 Changes in water bodies or the land No

5

surface Affecting drainage or run-off?

1.25 Transport of personnel or materials for

construction, operation or

decommissioning?

Yes By road only.

1.26 Long-term dismantling or decommissioning

or restoration works?

No

1.27 Ongoing activity during decommissioning

which could have an impact on the

environment?

No

1.28 Influx of people to an area either

temporarily or permanently?

No

1.29 Introduction of alien species? No

1.30 Loss of native species or genetic diversity? No

1.31 Any other actions? No

2. Use of Natural resources for construction or operation of the Project (such as land, water,

materials or energy, especially any resources which are non-renewable or in short supply):

Sr.

No.

Information/checklist confirmation Yes/No Details there of (with approximate

quantities frates, wherever possible) with

source of information data

2.1 Land especially undeveloped or agricultural

land (ha)

No

2.2 Water (expected source & competing users)

unit: KLD

Yes Water requirement will meet through the

ground water. For detail water balance

please refer Annexure – IV

2.3 Minerals (MT) No 2.4 Construction material - stone, aggregates,

and / soil (expected source - MT)

Yes Construction materials, like steel, cement,

crushed stones, sand, rubble, etc. required

for the project shall be procured from the

local market of the region.

2.5 Forests and timber (source - MT) No.

2.6 Energy including electricity and fuels (source,

competing users) Unit: fuel (MT), energy

(MW)

Yes Please refer Annexure – VII

2.7 Any other natural resources (use appropriate

standard units)

No

3. Use, storage, transport, handling or production of substances or materials, which could be harmful to human health or the environment or raise concerns about actual or perceived

risks to human health.

Sr.

No.

Information/Checklist confirmation Yes/No Details there of (with approximate

quantities/rates, wherever possible) with


3.1 Use of substances or materials, which are

hazardous (as per MSIHC rules) to human

health or the environment (flora, fauna, and

water supplies)

Yes For details please refer Annexure – IX

6

3.2 Changes in occurrence of disease or affect

disease vectors (e.g. insect or water borne

diseases)

No

3.3 Affect the welfare of people e.g. by changing

living conditions?

Yes Direct/Indirect employment

3.4 Vulnerable groups of people who could be

affected by the project e.g. hospital patients,

children, the elderly etc.

No

3.5 Any other causes No

4. Production of solid wastes during construction or operation or decommissioning (MT/month)

Sr.

No.

Information/Checklist confirmation Yes/No Details there of (with approximate

quantities/rates, wherever possible)


4.1 Spoil, overburden or mine wastes No

4.2 Municipal waste (domestic and or commercial

wastes)

No

4.3 Hazardous wastes (as per Hazardous Waste

Management Rules)

Yes Please refer Annexure –VI

4.4 Other industrial process wastes No

4.5 Surplus product No

4.6 Sewage sludge or other sludge from effluent

treatment

Yes

Please refer Annexure – VI

4.7 Construction or demolition wastes No

4.8 Redundant machinery or equipment No

4.9 Contaminated soils or other materials No

4.10 Agricultural wastes No

4.11 Other solid wastes Yes Please refer Annexure –VI

5. Release of pollutants or any hazardous, toxic or noxious substances to air (Kg/hr)

Sr. No. Information/Checklist confirmation Yes/No Details there of (with approximate



5.1 Emissions from combustion of fossil fuels

from stationary or mobile sources

Yes For details Please refer Annexure – VIII

5.2 Emissions from production processes Yes For details Please refer Annexure – VIII

5.3 Emissions from materials handling storage or

transport

Yes For details Please refer Annexure – VIII

5.4 Emissions from construction activities

including plant and equipment

No

5.5 Dust or odors from handling of materials

including construction materials, sewage and

waste

No

5.6 Emissions from incineration of waste No

7

5.7 Emissions from burning of waste in open air

(e.g. slash materials, construction debris) No

5.8 Emissions from any other sources No

6. Generation of Noise and Vibration, and Emissions of Light and Heat:



with source of information data with


6.1 From operation of equipment e.g. engines,

ventilation plant, crushers

Yes The Noise level will be within the

prescribed limit. At noisy areas adequate

preventive & control measures will be

taken. No significant noise, vibration or

emission of light & heat from the unit.

6.2 From industrial or similar processes Yes -do-

6.3 From construction or demolition No

6.4 From blasting or piling No

6.5 From construction or operational traffic No

6.6 From lighting or cooling systems Yes Adequate Lighting is provided in unit

and also local ventilation system is

provided.

6.7 From any other sources No

7. Risks of contamination of land or water from releases of pollutants into the ground or into

sewers, surface waters, groundwater, coastal waters or the sea:


quantities/rates, wherever possible) with


7.1 From handling, storage, use or spillage of

hazardous materials

Yes For details please refer Annexure – VI

7.2 From discharge of sewage or other effluents

to water or the land (expected mode and

place of discharge)

Yes For details please refer Annexure – V

7.3 By deposition of pollutants emitted to air into

the and or into water

No

7.4 From any other sources No

7.5 Is there a risk of long term build up of

pollutants in the environment from these

sources?

No

8

8. Risk of accidents during construction or operation of the Project, which could affect human

health or the environment




8.1 From explosions, spillages, fires etc. from

storage, handling, use or production of

hazardous substances

Yes For detail please refer Annexure – IX

8.2 From any other causes No

8.3 Could the project be affected by natural

disasters causing environmental damage

(e.g. floods, earthquakes, landslides,

cloudburst etc)?

No

9. Factors which should be considered (such as consequential development) which could lead to

environmental effects or the potential for cumulative impacts with other existing or planned

activities in the locality

(II) Environmental Sensitivity

Sr.

No.

Areas Name/

Identity

Aerial distance (within 15km.) Proposed project

location boundary

1 Areas protected under international conventions,

national or local legislation for their ecological,

landscape, cultural or other related value

- No protected area within 5 km from the

proposed expansion project boundary

Sr. No.

Information/Checklist confirmation

Yes/No

Details there of (with approximate



9.1 Lead to development of supporting. lities, ancillary development or development stimulated by the project which could have impact on the environment e.g.

• Supporting infrastructure (roads, power supply, waste or waste water treatment, etc.)

housing development extractive industry supply industry other

Yes For detail please refer Annexure – X

9.2 Lead to after-use of the site, which could

have an impact on the environment

No

9.3 Set a precedent for later developments No

9.4 Have cumulative effects due to proximity to

other existing or planned projects with

similar effects

No

9

2 Areas which important for are or sensitive Ecol

logical reasons - Wetlands, watercourses or other

water bodies, coastal zone, biospheres, mountains,

forests

Vishwamitri

river

Pawagadh

Mountain

Vishwamitri river is around 1 Km away from the

project site.

Pawagadh Mountain is around 5 Km away from

the project site.

3 Area used by protected, important or sensitive

Species of flora or fauna for breeding, nesting,

foraging, resting, over wintering, migration

- No protected area or sensitive species within 5

km from the proposed expansion project

boundary

4 Inland, coastal, marine or underground waters

- Vishwamitri river is around 1 Km away from the

project site.

5 State, National boundaries

- N.A.

6 Routes or facilities used by the public for access to

recreation or other tourist, pilgrim areas

- N.A.

7 Defense installations - N.A.

8 Densely populated or built-up area Halol Halol is around 10 km from the proposed

expansion project site.

9 Area occupied by sensitive man-made land uses

Hospitals, schools, places of worship, community

facilities)

- N.A.

10 Areas containing important, high quality or scarce

resources (ground water resources, surface

resources, forestry, agriculture, fisheries, tourism,

minerals)

- N.A.

11 Areas already subjected to pollution

environmental damage. (those where existing legal

environmental standards are exceeded)or

- N.A.

12 Are as susceptible to natural hazard which could

cause the project to present environmental

problems (earthquake s, subsidence ,landslides,

flooding erosion, or extreme or adverse climatic

conditions)

- N.A.

IV). Proposed Terms of Reference for EIA studies: For detail please refer Annexure – XI

11

LIST OF ANNEXURES

Sr.

No.

Name of Annexure Page Nos.

I List of Products along with capacities (Existing & Proposed)

&

List of Raw Materials along with capacities (Existing & Proposed)

12-13

14-41

II Plant Layout (Existing & Proposed) 42-43

III Brief Manufacturing Process (Existing & Proposed) 44-281

IV Water Consumption & Wastewater Generation (Existing & Proposed) 282-285

V Wastewater Treatment (Existing & Proposed) 286-293

VI List of Hazardous Waste (Existing & Proposed) 294-295

VII Details of Power & Fuel Requirements (Existing & Proposed) 296

VIII Details of Stack & Vents (Existing & Proposed) 297-298

IX Storage Details of Hazardous Chemicals (Existing & Proposed) 299-301

X Socio - Economic Impacts 302

XI Proposed Terms of Reference for EIA Studies 303-304

XII Plot Allotment Letter 305-335

XIII Copy of Water Supply Letter (Existing & Proposed) 336-339

XIV Membership Certificate of Common Facilities (Existing & Proposed) 340-352

XV Copy of Toposheet 353

XVI Copy of Valid CCA & its Compliance 354-364

XVII Copy of EC & its Compliance 365-381

12

ANNEXURE – I

LIST OF PRODUCTS

Sr.

No.

Product CAS Nos. LD50 (mg/kg) Existing

(MT/Month)

Additional

Proposed

(MT/Month)

Total after

Proposed

Expansion

(MT/Month)

1 Candesartan Cilexetil 139481-59-7 2 g/kg 25 + 175 200

2 Celecoxib 169590-42-5 2000 mg/kg

3 Irbesartan 138402-11-6 200 mg

4 Losartan Potassium - 29700 mg/kg

5 Methoxy Ethoxy Methyl Chloride

(MEM Chloride)

3970-21-6 3000 mg/kg

6 Moclobemide 71320-77-9 1300 mg/kg

7 Olmesartan 144689-63-4 2750 mg/kg

8 Ropinorole 91374-21-9 5 mg/kg

9 Valsartan 137862-53-4 600 mg/kg

10 Bupropion Hydrochloride 31677-93-7 300 mg/kg

11 Etoricoxib 202409-33-4 1499 mg/kg

12 O Des Venlafaxine 93413-62-8 10000 mg/kg

13 Fenofibrate 49562-28-9 2000 mg/kg

14 Lacosamide 175481-36-4 253 mg/kg

15 Mexilietien 5370-01-4 500 mg/kg

16 Telmisartan 144701-48-4 200 mg/kg

17 Venlafexine Hydrochloride Form B 99300-78-4 1000 mg/kg

18 Venlafexine Hydrochloride Form C - 1000 mg/kg

19 Fluoxetine Hydrochloride 56296-78-7 452 mg/kg

20 Metoprolol Succinate 98418-47-4 4000 mg/kg

21 Metoprolol Tartarate 67-64-1 3000 mg/kg

22 Azilsartan 91526-18-0 30 mg/kg

23 Bazedoxifene 51388-20-6 4000 mg/kg

24 Bosentan 150728-13-5 2.2676 mol/kg

25 Agomelatine - 10 mg/kg

26 Aripiprazole - 2.8894 mol/kg

27 Asenapine - 2.7083 mol/kg

28 Dronedarone 141626-36-0 2000 mg/kg

29 Darifenacin 133099-04-4 2000 mg/kg

30 Dabigatran 211914-51-1 2.7093 mol/kg

31 Donepezil 20011-70-3 2000 mg/kg

32 Warfarin HCl 5543-58-8 323 mg/kg

33 Febuxostat 144060-53-7 600 mg/kg

34 Felodipine 72509-76-3 2390 mg/kg

35 Fesoterodine Fumarate 286930-03-8 10,000 mg/kg

36 Iloperidone 133454-47-4 64 mg/kg

37 Minodronic Acid 180064-38-4 -

38 O-Desmethyl Venlafaxine Succinate 93413-62-8 2000 mg/m3

39 Nisoldipine 63675-72-9 1257 mg/kg

40 Prasugrel HCl 389574-19-0 2,000 mg/kg

41 Rabeprazole Sodium 117976-90-6 2.4215 mol/kg

42 Rivaroxaban 366789-02-8 980 mg/kg

43 Silosodine 160970-54-7 800 mg/kg

13

44 Tadalafil 171596-29-5 2000 mg/kg

45 Ticagrelor 274693-27-5 2,000 mg/kg

46 Vilazodone Hydrochloride 163521-08-2 2.6208 mol/kg

47 Warfarin Clathrate 67430-45-9 -

48 Vortioxetine Hydrobromide 960203-27-4 -

49 Solifenacin Succinate 242478-38-2 980 mg/kg

50 Canagliflozin 842133-18-0 -

51 Apixaban 503612-47-3 1000 mg/kg

52 Dapagliflozin 461432-26-8 750 mg/kg

53 Ivabradine 155974-00-8 840 mg/kg

54 Modafinil 68693-11-8 2.0926 mol/kg

55 Leflunomide 75706-12-6 235 mg/kg

56 Rivastigmine Tartrate 129101-54-8 400.43 µg/kg

57 Topiramate 97240-79-4 1,500 mg/kg

58 Linezolide 165800-03-3 7500 mg/kg

59 Lercanidipine Hydrochloride 132866-11-6 2.8614 mol/kg

60 Levetiracetam 102767-28-2 1000 mg/kg

61 Memantine Hydrochloride 41100-52-1 328-370

mg/kg

62 Alogliptin Benzoate 850649-62-6 2.5603 mol/kg

63 Apremilast 608141-41-9 980 mg/kg

64 Brexpiprazole 913611-97-9 -

65 Duloxetine Hydrochloride 136434-34-9 279 mg/kg

66 Empagliflozin 864070-44-0 5,000 mg/kg

67 Lamotrigine 84057-84-1 205 mg/kg

68 Linagliptin 668270-12-0 980 mg/kg

69 Lurasidone Hydrochloride 367514-88-3 2.4051 mol/kg

70 Macitentan 441798-33 -

71 Pregabalin 148553-50-8 1600 mg/kg

72 Riociguat 625115-55-1 56 mg/kg

73 Sofosbuvir 1190307-88-0 -

74 Teriflunomide 108605-62-5 -

75 Vardenafil HCl Trihydrate 330808-88-3 3000 mg/kg

76 Ivacaftor 873054-44-5 200 mg/kg

77 Nabumetone 42924-53-8 2380 mg/kg

78 Nitazoxanide 55981-09-4 1.7902 mol/kg

79 Lansoprazole 103577-45-3 5000 mg/kg

80 Entacapone 130929-57-6 2.6750 mol/kg

81 Daclatasvir 1009119-64-5 -

82 Elvitegravir 697761-98-1 56 mg/kg

83 Sacubitril Calcium 1369773-39-6 10,048 mg/kg

84 Tenofovir 147127-20-6 2.4903 mol/kg

85 Lumacaftor 936727-05-8 -

86 Ledipasvir 1256388-51-8 56 mg/kg

87 Deferasirox 201530-41-8 3000 mg/kg

Total 25 175 200

14

LIST OF RAW MATERIALS

SR.

NO.

NAME OF RAW MATERIAL QUANTITY

(Kg/Kg PRODUCT)

CAS Nos.

1 Candesartan Cilexetil

Methylene dichloride 28.30 75-09-2

Conc. Hydrochloric acid 1.28 7647-01-0

Methanol 8.43 67-56-1

Sodium Bicarbonate 1.15 144-55-8

Hyflo 0.11 61790-53-2

Sodium chloride 0.53 7647-14-15

Denatured Alcohol 1.03 64-17-5

Cyclohexane 8.95 110-82-7

Acetone 22.3 67-64-1

Dimethyl formamide 1.98 68-12-2

Anhydrous Potassium Carbonate 0.24 584-08-7

Cyclohexyl 1-chloro ethyl carbonate 0.36 99464-83-2

Triethyl amine 0.23 121-44-8

Triethyl Chloride 0.57 76-83-5

Sodium Azide 0.47 26628-22-8

Tri-n-butyl tin chloride 2.35 1461-22-9

O-Xylene 10.35 95-47-6


EBC-II 1.18 26968-58-1

Sodium Hydroxide 0.47 1310-73-2

Activated Charcoal 0.06 7440-44-0

Hyflow 0.02 61790-53-2

Hydrochloric Acid 1.41 7647-01-0

2 Celecoxib

IPA 9.28 67-63-0

Sulphonamido Phenyl hydrazine hydrochloride 0.85 17852-52-7

Methanol 0.39 67-56-1

Toluene 2.89 108-88-3

Sodium Methoxide 0.49 124-41-4

4-Methyl Acetophenone 0.61 122-00-9

Sulphuric acid 0.44 7664-93-9

Acetic acid 0.02 64-19-7

Trifluoroacetic acid 0.93 76-05-1

Absolute alcohol 0.46 64-17-5

Sulfuric acid 1.77 7664-93-9

3 Irbesartan

Toluene 4.13 108-88-3

O-Xylene 0.01 1330-20-7

Triethyl amine Hydrochloride 1.67 554-68-7

Sodium Azide 0.51 26628-22-8

Sodium hydroxide 0.45 1310-73-2

Methyl t-butyl ether (MTBE 1.32 628-28-4

Sodium Nitrite 0.33 7631-99-4

Hydrochloric acid 1.57 7647-01-0

Denatured Ethyl Alcohol 10.91 64-17-5

Activated charcoal 0.02 7440-44-0

Hyflow 0.01 61790-53-2


15

Acetone 4.06 108-88-3

4-Bromomethyl -2- Cyano biphenyl (4-BMCP) 1.15 114772-38-2

2-Butyl-1, 3 -diazaspiro [4, 4] non -1-en-4-one hydrochloride 1.00 97-76-4

Sodium Chloride 0.23 7647-14-15

MTBE 0.85 7440-44-0

4 Losartan Potassium

Methanol 3.06 67-56-1

Potassium Hydroxide 0.18 1310-58-3

Activated Carbon 0.11 7440-44-0

Hyflow 0.03 61790-53-2

Acetone 5.56 67-64-1

Toluene 1.64 108-88-3.

N Methyl Pyrolidine 0.49 872-50-4

Sodium Azide 0.45 26628-22-8

Triethyl Amine Hydrochloride 0.94 554-68-7

Cyano alcohol 0.94 1310-73-2


Carbon 0.05 7440-44-0

Sulphuric Acid 0.69 7664-93-9


5 Methoxy Ethoxy Methyl Chloride

Para Formaldehyde 0.333 30525-89-4

Methyl Cellosove 0.867 109-86-4

Thionyl Chloride 1.433 2125597

D M Water 22.222 7732-18-5

Sodium Hydroxide Lye (50%) 1.667 1310-73-2

6 Moclobemide

2-Chloro Ethylamine Hydrochloride 1.327 870-24-6

4- Chloro Benzoyl Chloride 0.270 122-01-0


D M Water 0.010 7732-18-5

Dichloromethane 1.340 75-09-2

Hyflow 0.980 61790-53-2

Isopropyl Alcohol 0.010 67-63-0

Moclobemide Stage-I 0.180 71320-77-9

Moclobemide Stage-II 0.160 71320-77-9

Moclobemide Stage-III 0.190 71320-77-9

Morpholine 0.180 71320-77-9 Sodium bicarbonate 0.260 144-55-8

Sodium Carbonate 0.040 1545739


Toluene 0.030 108-88-3

Toluene 2.370 108-88-3


7 Olmesartan

Acetone 14.25 67-64-1


Hyflow 0.05 61790-53-2


Methanol 6.95 67-56-1



Ethyl Acetate 12.66 141-78-6

N,N-Dimethyl formamide 6.26 68-12-2

16

Sodium hydroxide powder 0.11 1310-73-2

Anhydrous Potassium Carbonate powder 0.24 584-08-7

Medoxomil 0.36 144689-63-4



N,N-Dimethyl formamide 5.96 68-12-2

Anhydrous potassium carbonate powder 0.95 584-08-7

Ethyl-4-(1-hydroxyl-1-methylethyl)-2-propylimidazole-5-

carboxylate 0.47

144689-93-0

5-[4’-(Bromomethyl) [1, 1’-biphenyl]-2-yl]-2-(triphenylmethyl)-2H-

tetrazole (TTBB) 1.05

133051-88-4


8 Ropinorole

Tetra Hydro Furan 2.61 109-99-9

Sodium Borohydride 0.36 16940-66-2

2-Methyl -3-Nitro phenyl acetic acid (Stage II) 0.74 644-36-0

Methane Sulphonic Acid 0.36 75-75-2

Methanol 1.79 67-56-1



Sodium bicarbonate 0.18 144-55-8


Tri- ethyl amine 3.84 121-44-8

p-Toluene Sulfonyl chloride 1.01 98-59-9


Di-n-propyl-amine 1.06 142-84-7

Toluene 0.96 108-88-3


Oxalic Acid Dihydrate 0.38 144-62-7

9 Valsartan

Process Water 72.78 7732-18-5

Potassium carbonate 1.75 584-08-7

O-Xylene 7.88 95-47-6

Valeroyl Chloride 0.75 638-29-9




Tri n-butyl tin chloride (TBTC) 2.95 1461-22-9

Sodium Azide 0.71 26628-22-8


Tetra butyl ammonium bromide 0.07 1643-19-2


Carbon 0.13 7440-44-0

Hyflo 0.12 61790-53-2

Methanol 1.74 67-56-1

L-Valine 0.44 13734-41-3

Thionyl Chloride 1.32 7719-09-7

4-Bromomethyl 2 Cyno Bi Phenyl 0.79 114772-54-2

Toluene 0.76 108-88-3


Potassium Carbonate 0.49 584-08-07

Potassium Iodide 0.04 7681-11-0

Acetone 4.28 108-88-3

Oxalic Acid 0.41 6153-56-6

17

10 Bupropion Hydrochloride


Methanol 3.64 67-56-1

Hyflo 0.01 61790-53-2


3’Chloro-propiophenone 0.77 936-59-4

Bromine 0.81 7726-95-6

Methanol 0.09 67-56-1

Sodium Thiosulphate 0.06 7772-98-7

Toluene 10.00 108-88-3


t-Butyl Amine 1.67 75-64-9

IPA HCL 1.10 7647-01-0

11 Etoricoxib

Toluene 13.51 108-88-3

Ammonia solution 1.48 1336-21-6

IPA 36.55 67-63-0

Hexane 0.41 110-54-3

Activated carbon 0.06 7440-44-0

Hyflow 0.09 61790-53-2

Etoricoxib Form- I 0.001 202409-33-4

Propionic acid 6.19 79-09-4


1-(6-methylpyridin-3-yl)-2-[4-(methyl sulfonyl) phenyl] ethanone

(Ketosulfone) 1.25

221615-75-4

MSA 0.83 75-75-2

Conc. HCl 0.30 7647-01-0

Toluene 21.68 108-88-3


Hydroxyl amine Hydrochloride 0.18 5470-11-1


Hyflo 0.11 61790-53-2

IPA. HCl 2.00 7647-01-0

Methanol 25.74 67-56-1

IPA 11.43 67-63-0

Ammonia 1.22 1336-21-6

CDT Phosphate 3.64 249561-98-6

Conc. HCL 1.87 7647-01-0

Toluene 0.61 108-88-3


12 O Des Venlafaxine

Acetone 7.6 108-88-3

DM Water 5.4 7732-18-5

Succinic Acid 0.3 110-15-6


Methanol 34.74 67-56-1


Hyflo 0.05 61790-53-2

Methanol 2.06 67-56-1


Sodium Hydride 0.69 7646-69-7

Ethanethiol 0.91 75-08-1

Venlafaxine Hydrochloride 1.33 99300-78-4


18


Toluene 4.63 108-88-3



13 Fenofibrate

Isopropyl alcohol 5.15 67-63-0


Methylene chloride 4.54 75-09-2



Hyflo 0.01 61790-53-2

Acetone 5.38 67-64-1

4-chloro-4-Hydroxy Benzo Phenone (4-CHBP) 0.93 42019-78-3


Chloroform 1.19 67-66-3


14 Lacosamide


Conc. HCl 3.04 7647-01-0

DM Water 14.93 7732-18-5



Acetic anhydride 0.59 108-24-7


Hyflo 0.04 68855-54-9

IPA 3.87 67-63-0

n-Heptane 11.23 142-82-5


Toluene 5.84 108-88-3


Tetra-butyl Ammonium Bromide 0.21 1643-19-2

Dimethyl Sulphate 1.16 77-78-1



15 Mexiletine HCl

Methanol 5.70 67-56-1

10-15% Methanolic HCl 4.00 7647-01-0


Hyflo 0.02 68855-54-9

Acetone 6.60 67-64-1

Methanol 6.63 67-56-1

Raney Nickel 0.07 12635-27-7

Hydrogen 0.08 1333-74-0

Hyflo 0.11 68855-54-9

MDC 6.15 75-09-2

HCl 0.79 7647-01-0


Toluene 4.01 108-88-3


Acetone 5.52 67-64-1

2, 6-dimethyl Phenol 0.77 576-26-1



Chloroacetone 0.64 78-95-5

19

Toluene 4.81 108-88-3



Sodium carbonate 1.01 497-19-8

Hydroxylamine Hydrochloride 0.48 5470-11-1

16 Telmisartan

Methanol 10.14 67-56-1



Hyflo 0.02 68855-54-9


Liq. Ammonia 0.12 7664-41-7

Acetone 4.44 67-64-1

2-N-Propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)

benzimidazole 0.67

152628-02-9


Methyl-4-(Bromomethyl)-biphenyl-2-carboxylate 0.73 114772-38-2

17 Venlafexine Hydrochloride Form B

n-Propanol 2.6 71-23-8


Hyflo 0.0024 68855-54-9

Seed material 0.0002 -

n-Propanol 2.6 71-23-8


Raney Nickel 0.11 12635-27-7

Methanol 1.95 67-56-1

Activator 0.03 -

Hydrogen gas 0.03 1333-74-0

Hyflo 0.05 68855-54-9

Formic Acid 1.37 64-18-6



Formaldehyde 0.87 50-00-0.

Toluene 4.57 108-88-3

Ethyl acetate 0.09 141-78-6

IPA 3.78 67-63-0

IPA. HCl 0.80 -

Methanol 0.87 67-56-1

Ammonia 0.16 7664-41-7

Methanol 2.17 67-56-1

Methoxy Phenyl Acetonitrile 0.69 104-47-2

Sodium Hydroxide flakes 0.22 1310-73-2

Cyclohexanone 0.64 108-94-1

Super Base 0.19 -

Toluene 2.15 108-88-3

Methanol 2.17 67-56-1



18 Venlafexne Hydrochloride Form C

IPA 5.57 67-63-0


Hyflo 0.01 68855-54-9

VNS-II seed 0.00 -

IPA 5.57 67-63-0

20


Hyflo 0.01 68855-54-9

VNS-II seed 0.00 -

Raney Nickel 0.10 12635-27-7

Methanol 1.66 67-56-1

Activator 0.03 -


Hyflo 0.04 68855-54-9

Formic Acid 1.17 64-18-6



Formaldehyde 0.74 50-00-0

Toluene 3.89 108-88-3


IPA 3.22 67-63-0

IPA. HCl 0.68 -

Methanol 0.87 67-56-1

Ammonia 0.16 7664-41-7

Methanol 2.17 67-56-1



Cyclohexanone 0.64 108-94-1

Super Base 0.19 -

Toluene 2.15 108-88-3

19 Fluoxetine Hydrochloride

Methanol 0.43 67-56-1

Dimethyl Sulphoxide 3.30 67-68-5


4-Chlorobenzo Trifluoride 0.87 98-56-6


Toluene 4.05 108-88-3

Eno Carbon 0.03 7440-44-0

Hyflo 0.01 68855-54-9

Hydrochloric acid gas 0.12 7647-01-0


3-Chloro-1-Phenyl Propanol (3-CPPA) 1.32 100306-33-0

Methanol 0.05 67-56-1

40% Aqueous Methyl Amine solution 9.44 74-89-5

Sodium Iodide 0.06 7681-82-5


Toluene 14.83 108-88-3

20 Metoprolol Succinate

Acetone 27.15 67-64-1

Hyflo 0.03 68855-54-9


Succinic acid 0.14 110-15-6

Epichlorohydrin 0.69 106-89-8

4-(2-Methoxyethyl) Phenol 0.65 56718-71-9


Concentrated HCL 0.71 7647-01-0

Mono-isopropyl amine 3.59 75-31-0

Toluene 7.00 108-88-3

Hyflo 0.01 68855-54-9

21 Metoprolol Tartarate

21

Acetone 31.22 68855-54-9

Hyflo 0.03 7440-44-0


Tartaric Acid 0.16 106-89-8

Epichlorohydrin 0.69 56718-71-9

4-(2-Methoxyethyl) Phenol 0.65 1310-73-2


Concentrated HCL 0.71 75-31-0

Mono-isopropyl amine 3.59 108-88-3

Toluene 7.00 68855-54-9

Hyflo 0.01 147403-03-0

22 Azilsartan

4-hydroxymethyyl-5-methyl-1,3-dioxol-2-one(KRM) 0.491 64-19-7

Acetic Acid 0.173 541-41-3

ECF 0.558 7647-01-0

hydrochloric acid 1.051 5470-11-1

Hydroxyl Amine-HCI 4.233 -

KSM 2.505 3164-85-0

Potassium Ethyl Hexonate 0.398 584-08-7


p-TSCI 0.636 497-19-8

Sodium Carbonate 6.462 1310-73-2

Sodium Hydroxide 0.415 -

Stage I 2.079 -

Stage II 1.622 -

Stage III 1.103 -

Stage IV 1.136 198481-32-2

23 Bazedoxifene

(Benzyloxy)Aniline Hydrochloride(Amine, 2.147 35081-45-9

(Benzyloxy)phenyl]-2-bromopropan-1-one (Bromo 1.167 -

(Chloro Methyl)Phenoxy]ethyl}azepane 1.082 120-72-9

[4-(Benzyloxy)phenyl]-3-methyl-indole(Indole) 0.992 100-02-7

4-Nitrophenol(P-Nitro phenol) 0.819 198479-63-9

5-(Benzyloxy)-2-[4-(phenyl)phenyl]-3-methyl 1.538 64-19-7

Acetic Acid 0.138 7440-44-0


Anhydrous Ferric Chloride 0.012 584-08-7


Benzyl chloride 0.729 1145-76-2

Benzyl-4-nitrophenylether(Nitro compound) 1.228 7803-57-8

Hydrazine Hydrate 0.860 7647-01-0


Hydrogen 0.015 7681-11-0


Sodium-Tert Butoxide 0.909 121-44-8

Triethylamine 0.924 147536-97-8

24 Bosentan

4,6-Dichloro-5-(2-Methoxyphenoxy)-2,2-Bipysimidine 0.726 150728-13-5

4-Tert-Butylbenzene Sulfonamide 0.443 6292-59-7

BOS / I (Crude) 1.053 -

BOS / I (Pure) 1.000 -

BOS / II 1.053 -

BOS / IV 1.053 -

Ethylene Glycol 12.339 107-21-1

22



Water 8.421 7732-18-5

25 Agomelatine

2-(7-methoxy -1-napthyl)ethylamine hydrochloride 1.000 -

2-(7-methoxy-1-napthyl) Acetonitrile/ Agomelatine 1.000 -

Acetic Anhydrous 0.510 108-24-7

Hydrogen Gas 0.020 1333-74-0

Isopropyl Alcohol HCL 0.740 -

Sodium Acetate Anhydrous 0.420 127-09-3

26 Aripiprazole

7-Hydro-3,4-dihydro2(1H)quinolinone 0.921 -

1-(2,3-Dichlorophenyl)Piperazine hydrochloride 1.022 -

1-bromo--chlorobutane 1.933 6940-78-9

Acetonitrile 5.524 75-05-08



DM Water 58.922 7732-18-5

DMAc 3.683 127-19-5

DMF 4.602 68-12-2

Ethyl alcohol 23.941 64-17-5

Hyflo 0.110 68855-54-9




Stage I 0.987 -

Stage II 1.065 -

Stage IIA 0.893 -

Stage III 1.160 -

7-Hydro-3,4-dihydro2(1H)quinolinone 0.921 -

1-(2,3-Dichlorophenyl)Piperazine hydrochloride 1.022 -

1-bromo--chlorobutane 1.933 6940-78-9


27 Asenapine

Ammonium Hydroxide 74.716 1336-21-6

Cesium Carbonate 8.159 534-17-8

CuCI2.(H2O)2 9.450 10125-13-0

Cuprous chloride 2.375 7758-89-6

Fumic Acid 1.308 110-17-8

Hydro Chloric Acid 11.304 7647-01-0

Hydrogen Gas 0.034 1333-74-0

Maleic Acid 0.456 110-16-7

N,N-Dimethyl Glycine hydrochloride 1.747 2491-06-7

NH4OH 18.571 1336-21-6

Nitro Oxepine 1.701 -


Sodium Sulphite 6.899 7757-83-7

Trans-N-methyl-4-(2-bromophenyl)-3-(2-hydro-5-nitrophenyl) 4.725 -


CuCI2.(H2O)2 9.450 10125-13-0

Cuprous chloride 2.375 7758-89-6

Fumic Acid 1.308 110-17-8

28 Dronedarone

1-Chloro-3-Dibutyl Amino propane 0.714 -

23

2-N-Butyl-3-(4-(3-Dibutylaminopropo)Benzoyl)-5-Nitrobenzofuran 1.610 -

2-N-Butyl-3-(4-(3-Dibutylaminopropoxy-benzoyl)-5-

Amonibenzofuran Dioxalate 1.626

-


Amonibenzofuran Pure 1.182

-


Amonibenzofuranamidobezofuran 1.371

-

2-N-Butyl-3-(4-Hydroxybenzoyl)-5-Nitrobenzofuran 1.073 -

Aq. Ammonia Solution 1.138 93372-25-9

Dronedarone HCl crude 1.220 141625-93-6

Ethyl Acetate HCl 1.283 -

Hydrogen Gas 0.016 1333-74-0

Methane Sulfonyl chloride 0.253 124-63-0

Oxalic Acid Dihydrate 1.294 6153-56-6


Pyridine 0.141 110-86-1

29 Darifenacin

KSM I 2.307 -

Sodium Hydroxide 0.551 1310--73-2

Stage IA 1.753 -


Tartaric Acid 0.771 147-71-7,

Stage I 1.429 -

KSM II 0.757 -


Hydrogen Bromide 0.300 10035-10-6

30 Dabigatran

1-Methyl-2-Pyrolidone 2.004 872-50-4

Acetic Acid 2.043 64-19-7

Ammonia 0.116 7664-41-7

DIPEA 1.278 7087-68-5

Hydrochloride 0.245 7647-01-0

KSM I 1.945 -

KSM II 1.101 -

Methane Sulfonic Acid 0.153 75-75-2

N-Hexyl Chloroformate 0.618 6092-54-2

Pivaloyl Chloride 0.920 3282-30-2

Stage I 1.634 -

Stage II 1.307 -

Stage III 1.111 -

Triethyl Amine 0.986 121-44-8

31 Donepezil

5,6-Dimethoxy 1-Indanone 1.380 2107-69-9

Benzyl bromide 1.349 100-39-0


Hydrogen Gas 0.014 1333-74-0

Pyridine-4-Caboxaldehyde 0.814 872-85-5

Sodium Borohydride 0.265 16940-66-2

sodium Hydroxide 0.025 1310-73-2

Stage I 1.228 -

Stage II 1.069 -

32 Warfarin Acid

Formamidinecetate 3.840 3473-63-0

KSM II 1.093 -

24

KSM-1 2.272 -

Oxalyl chloride 3.244 79-37-8

Stage I 1.886 -

Stage II 1.471 -

33 Febuxostate

KSM 1.547 -

Isobutyl Bromide 1.162 78-77-3


(Ethyl 2-(3-Formyl-4-Isobutoxyphenyl)-4-Methylthiazole-5-

Carboxylate)

1.470 -

Ammonium Hydroxide. HCl 0.323 -


(Ethyl 2-(3-Cyano-4-Isobutoxyphenyl)-4-Methyl-5-

thiazoleCarboxylate)

1.352 -



Stage III (Tech) 1.149 -

Acetone 0.750 67-64-1

34 Felodipine

2,3 Dichloro Benzaldehyde 0.667 6334-18-5

2,3 Dichlorobenzylidine Methylacetoacetate 1.000 -

3-Amino Crotonic acid Ethyl ester 0.630 -

Methyl Aceto Acetate 0.465 105-45-3

35 Fesoterodine Fumarate

Benzyl amine (Free base) 2.836 100-46-9

Benzyl amine DPTT 5.454 100-46-9

Benzylated Free Base(Inst) 2.585 -

Cerric Ammonium nitrate 12.544 16774-21-3

Dihydroxy Compound 1.017 -

Fesoterodine Base(Inst) 1.230 -

Fumaric Acid 1.477 110-17-8

Hydrogen gas 0.013 1333-74-0

Isobutyryl chloride 0.340 79-30-1

NaBH4 0.774 16940-66-2


Stage I 3.272 -

Stage I A 2.945 -

Stage I B 2.945 -


Water 0.109 7732-18-5

36 Iloperidone

2-Butyl-1,3-Diaziaspiro[4,4]non-1-en-4-one Hydrochloride 1.145 -

4-Bromomethyl 2-Cyno Biphenyl(4 BMCP) 1.316 1118-68-9

Acetone 4.648 67-64-1

D M Water 27.027 7732-18-5


Irbesartan-I 1.250 138402-11-6

Methyl T-Butyl Ether 1.879 1634-04-4

O-Xylene 0.009 95-47-6

Sodium Azide 0.538 26628-22-8



Sodium Nitrate 0.175 7631-99-4

Toluene 4.335 108-88-3

25

Triethyl Amine Hydrochloride 1.750 554-68-7

37 Minodronic Acid

2-Amino Pyridine 0.582 504-29-0

Chloro Acetaldehyde 0.983 107-20-0

Ethyl Oxalyl Chloride 1.479 4755-77-5


Hypochloric Acid 1.098 7790-92-3

PCI3 2.763 7719-12-2



Stage I 0.512 -

Stage II 0.950 -

Stage II A 0.947 -

Stage II B 0.824 -

Stage II C 0.766 -

Stage III 1.111 -

Water 0.691 7732-18-5

38 O-Desmethyl Venlafaxine Succinate

Acetone 7.6 67-64-1

DM Water 5.4 7732-18-5



Hyflow 0.1 68855-54-9

Methanol 36.80 67-56-1



Ethanethiol 0.91 75-08-1

Venlafaxine Hydrochloride 1.33 99300-78-4



Toluene 4.63 108-88-3


39 Nisoldipine

2-Nitrobenzaldehyde 0.625 552-89-6

2-Nitrobenzylidine Aceto acetic acid Isobutyl Ester 1.204 -

Isobutyl Acetoacetate 0.620 105-45-3

Methyl-3-Amino Crotonate 0.714 14205-39-1

40 Prasugrel Hydrochloride

2-Acetoxy-5-(Cyclopropylcarbonyl-2-Fluorobenzyl)-4,5,6,7-

Tetrahydrothieno[3,2-c] Pyridine Maleate

1.481 -

2-Oxe-(Cyclopropylcabonyl-2-Fluorobenzyl)-2,4,5,6,7,7a-

HexahydroThieno[3,2-C] Pyridine

1.299 -

5-Triphenylmethyl-2-Oxo-2,4,5,6,7,7a-Hexahydro Thieno[3,2-c]

Pyridine

1.804

Acetic Anhydride 1.533 108-24-7

Acetone 31.356 67-64-1


KSM Stage II 1.516 -

Maleic Acid 0.402 110-16-7


Stage I 0.866 -

Stage II 1.234 -

Stage III 1.111 -

41 Rabeprazole Sodium

26

2-Mercepto Benzimidazole 0.647 97963-62-7

RAB / Chloro 1.097 1163685-31-1

RAB / Hydroxy 1.097 131-57-7

RAB / I 1.316 146887-79-8

RAB / II 1.053 146887-79-8



Sodium Hypo chloride 4.054 7681-52-9


42 Rivaroxaban

(4-4-Aminophenyl)-morpholin-3-one 1.411 438056-69-0

4-Dimethylaminopyridine(DMAP) 0.007 1122-58-3

5-Chlorothiophene-2-cacoxylic acid 1.220 24065-33-6

Aq. Methyl Amine 1.627 74-89-5

CDI 4.034 530-62-1

DMF SKSM NDMF-ST-II 1.829 2491-06-7

DMF ST 1.968 2491-06-7

Glycidyl Phthalimide 1.637 5455-98-1


Oxalyl Chloride 1.495 79-37-8

Sodium Acetate 1.476 127-09-3

Stage I 2.187 -

Stage II 1.143 -

43 Silosodine

3-Chloropropano 1.000 109-70-6

Benzyl Bromide 1.664 100-39-0

Bromide 0.590 100-39-0

Copper Cyanide 0.240 544-92-3

DMF 383.9 68-12-2

Hydrogen Bromide 1.000 10035-10-6

Sodium Bromide 0.863 7647-15-6


Sodium meta Bisulphate 0.130 10034-88-5

Stage I 1.860 160970-54-7

Stage II 270.0 160970-54-7

Stage III 1.000 160970-54-7

Stage IV 1.000 160970-54-7

TBAB 0.000 1643-19-2

Water 1354.0 7732-18-5

44 Tadalafil

D-Tryptophan methyl ester hydrochloride 0.943 14907-27-8


Chloroacetyl chloride 0.754 79-04-9



DMAc 4.716 127-19-5


Hyflo 0.765 68855-54-9

Isopropanol 11.321 67-63-0

Methanol 25.309 67-56-1

Methylamine 1.047 593-51-1

Piperonal 0.613 120-57-0

Process water 65.532 7732-18-5


27

Sodium sulphate 0.528 7757-82-6

Stage I 1.198 171596-29-5

Stage I A 0.898 171596-29-5

Stage II 1.047 171596-29-5 Stage II A 1.141 171596-29-5

Toluene 3.302 108-88-3

45 Ticagrelor

DIPEA 2.085 7087-68-5


KSM-I 1.985 -

KSM-II 1.489 -




Stage I 1.886 -

Stage II 1.471 -

46 Vilazodone Hydrochloride

4-Chloro-N,N,2-Tri-Methyl-7-Quinolinamine 0.668 -

5-Nitrosalicyladehyd 0.726 97-51-8

Ammonia 0.110 7664-41-7

Bis(2-Chloroethyl)Amine HCl 0.950 821-48-7

Diethyl Bromo Malonate 0.835 685-87-0

Dimethyl Bromo Malonate 1.249 685-87-0

Hydrogen Chloride 0.091 7647-01-0

Hydrogen Gas 0.025 1333-74-0

Potassium Carbonate Powder 1.811 584-08-7

Stage I 1.044 -

Stage IIA 1.566 -

TBAB 0.115 1643-19-2

Trimethyl Amine 3.028 75-50-3

Vilazodone (Stage II) 1.143 163521-08-2

47 Warfarin Clathrate

2-Hydroxy Acetophenone 0.769 582-24-1

4-Hydroxy Coumarine 0.769 1076-38-6

Benzyl Acetone 0.693 1896-62-4

Diethyl Carbonate 1.000 105-58-8

Sodium Methoxide 0.762 124-41-4


48 Vortioxetine Hydrobromide

2,4-Dimethyl thiophenol 1.485 -

BOC Imino diacetic acid 1.663 -

Borane Dimethyl sulfide 1.257 13292-87-0

CDI 2.654 530-62-1

DMF 13.859 68-12-2


HBr 30.525 10035-10-6

Hexane 30.041 110-54-3


Iron 0.109 7439-89-6

MDC 22.873 75-09-2

O-Fluoro nitrobenzene 1.485 1493-27-2

Potassium Chromate 2.970 7789-00-6


St-I Intermediate 2.089 -

28

St-II Intermediate 1.376 -

St-III Intermediate 1.911 -

THF 49.258 109-99-9

Toluene 96.468 108-88-3

49 Solifenacin Succinate

(1S)-1-Phenyl-1,2,3,4-Tetrahydro Isoquinoline 0.800 118864-75-8

Ethyl Chloro Formate 0.436 541-41-3



R-(-)-3-Quinuclid Idol 0.608 -


Solifenacin Base 1.384 242478-37-1

Stage I 1.072 -


50 Canagliflozin

4-methyl Morpholine 44.412 109-02-4

5-(Flourophenyl)thiophene 10.580 1030825-20-7

5-Bromo-2-methyl benzoic acid 11.736 79669-49-1

Aluminium chloride 9.426 7446-70-0

Boron trifluoride ethyl etherate 41.421 109-63-7

Chlorotrimethylsilane 28.713 75-77-4


Gluconolactone 5.941 90-80-2

Methane Sulphonic acid 8.757 75-75-2

Methanol 73.077 67-56-1

N,N-dimethylaminopyridine 1.154 -

n-butyl lithium 16.359 109-72-8

Oxalyl chloride 5.772 79-37-8

Propionic Anhydride 10.771 123-62-6

Sodium methoxide 0.048 124-41-4

Stage I A 1.164 -

Stage I B 1.260 -

Stage II 1.135 -

Stage III 1.097 -

Stage IV 1.029 -

Stage IV A 1.318 -

Tetrahydrofuran 352.864 109-99-9

Triethylsilane 28.009 617-86-7

51 Apixaban

3-Morpholino-1-(4-(2-oxopiperidin-1-yl)phenyl)5,6-

dihydropyridin-2(1H)-one

1.935 -

4-Methoxy phenyl hydrazine hydrochloride 0.798 19501-58-7

Ammonia Solution 2.427 7664-41-7


Ethyl Oxalyl chloride 0.832 4755-77-5

Ethylene glycol 18.204 107-21-1

MDC 42.355 75-09-2

Methanol 25.747 67-56-1

Pyridine 0.522 110-86-1

Stage I 1.117 -

Stage I A 1.210 -

Stage II 1.311 -


52 Dapagliflozin

29

5-Bromo-2-chloro-4-ethoxy Diphenyl methane 2.453 461432-23-5

n-butyl lithium 5.886 109-72-8

4-Dimethylaminopyridine 0.029 1122-58-3



Borontrifluoride dfietherate 1.540 109-63-7

Delta gluconolactone 0.579 90-80-2

Methane Sulfonic acid 0.736 75-75-2

Methanol 9.813 67-56-1

N-methyl Morpholine 2.629 109-02-4

Pyridine 3.039 110-86-1

Stage I 1.207 -

Stage I A 1.089 -

Stage II 0.873 -

THF 30.503 109-99-9

Triethyl silane 1.697 617-86-7

Trimethyl silyl chloride 2.747 75-77-4

53 Ivabradine

1,3-Dihydro-7,8-dimethoxy-2H-3,3 Benzazapin 0.947 -


KSM II 0.321 -

Hydrogen Gas 0.475 1333-74-0

Potassium Tert Butoxide 0.533 865-47-4



Stage II 0.784 -

1-Bromo-3-Chloro propane 1.020 109-70-6

Stage I 1.188 -

Stage III 1.333 -

54 Modafinil

Process Water 42.15 7732-18-5

Thio Urea 0.36 62-56-6

Benzhydrol 0.73 91-01-0

Hydrobromic Acid 3.09 10035-10-6

Caustic Soda 0.64 1310-73-2

Chloroacetic Acid 0.43 79-11-8

HCl 1.82 7647-01


Sod Sulphate 0.15 7757-82-6

Hexane 1.87 110-54-3

Sod Bicarbonate 0.71 -

Methanol 3.21 67-56-1

Sulfuric Acid 0.27 7664-93-9

Ammonia gas 1.36 7664-41-7

DM Water 3.48 7732-18-5


Hydrogen Peroxide 0.16 7722-84-1

55 Leflunomide

Ethyl acetic acetate 2.31 141-78-6

Triethyl ortho formate 4.56 122-51-0



Hydroxylamine HCl 1.13 5470-11-1

Caustic soda 0.65 1310-73-2

30

Methanol 2.16 67-56-1


HCl 0.09 7647-01-0

MDC 10.70 75-09-2

Glacial Acetic Acid 1.47 64-19-7

IPA 0.36 67-63-0


Chloroform 5.92 67-66-3

TEA 0.66 121-44-8

Toluene 4.89 108-88-3

Acetone 0.97 67-64-1

Carbon 0.05 7440-44-0

Hyflo 0.03 68855-54-9

56 Rivastigmine Tartrate

3-hydroxy Acetophenone 2.54 121-71-1

Raney Nickel 0.01 12635-27-7

Para formaldehyde 2.78 30525-89-4

D(+) camphor Sulphonic acid 1.98 3144-16-9


Ammonia gas 1.70 7664-41-7


Sodium Sulphate 0.56 7757-82-6

Methanol 6.75 67-56-1


Ethyl alcohol 4.28 64-17-5

N-ethyl N-methyl carbamoyl chloride 2.04 42252-34-6

L(+) Tartaric acid 1.05 87-69-4


4-dimethylamino pyridine 2.39 1122-58-3

Toluene 7.28 108-88-3


57 Topiramate

Acetone 2.56 67-64-1

D-Fructose 3.85 57-48-7


Dichloro methane 12.89 75-09-2

Cyclo hexane 7.34 67-63-0

Iso propyl alcohol 3.95 67-63-0

Sulfuryl Chloride 2.35 110-82-7

Pyridine 3.25 110-86-1

Citric Acid solution 0.46 77-92-9



THF 5.24 109-99-9

Calcium Chloride 2.88 7440-70-2

Ammonia gas 1.06 7664-41-7


Methanol 12.08 67-56-1

DM water 15.23 7732-18-5


58 Linezolide

Sodium Azide 0.304 26628-22-8

Methanol 0.00 67-56-1

Dimethyl Formamide 3.750 68-12-2

31


(R)-[N-3-(3-Fluoro-4-MORF)] 1.250 -

HCl 0.00 7647-01-0

Sodium Nitrate 0.00 7631-99-4

Linezolide-II


Purified siliceous earth 0.68 -

toluene 9.831 108-88-3

Acetone 20.339 67-64-1

Methanol 6.780 67-56-1

10% Palladium Charcoal 0.092 7440-05-3


Acetic Anhydride 0.505 108-24-7


Hydrogen Gas 0.610 1333-74-0

Nitrogen Gas 1.661 7727-37-9

Silica Gel 0.847 112926-00-

Linezolide stage-I 1.11525 165800-03-3

10% Palladium Charcoal 0.010 -



Dilute Acetone line 1.098 67-64-1

Dilute Methanol line 1.728 67-56-1

Dilute Toluene line 2.110 108-88-3


Recovered Acetone line 6.076 67-64-1

Recovered Ethyl acetate 46.026 141-78-6

59 Lercanidipine Hydrochloride

2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-1,4-

dihydropyridine-3-carboxylic acid

3.55 -

2,N-dimethyl-N-(3,3-diphenyl-propyl)-1-amino-2-propanol 2.76 100442-33-9

Di cyclohexylcarbodiimide 1.82 538-75-0

4-Dimethyl aminopyridine 2.07 1122-58-3



Toluene 5.36 108-88-3

Ethanol 2.88 64-17-5

60 Levetiracetam

Sodium Sulphate 1.14 7757-82-6

S9+) 2-Amino-Butryramide 1.14 7682-20-4

Tetra Butyl Ammonium Bromide 0.057 1643-19-2

4-Chloro Butyryl Chloride 1.51 4635-59-0

Potassium Hydroxide powder 2.87 1310-58-3




Hyflo 0.48 68855-54-9

Glacial Acetic Acid 0.05 64-19-7

61 Memantine Hydrochloride

1-Bromo-3, 5- Dimethyladamantane 2.13 941-37-7




Toluene 16.26 108-88-3

32

Sodium Hydrosulfite 0.02 7775-14-6


Memantine hydrochloride-II 41100-52-1

Polyethylene Glycol-400 5.73 25322-68-3

Satge-1 1.43 -


Toluene 42.34 108-88-3



Hyflo 2.15 68855-54-9


Memantine hydrochloride-III -


Stage-2 1.25 -


Hyflo 0.06 68855-54-9

62 Alogliptin Benzoate

3-methyl-6-chlorouracil 1.0 -

N-methyl pyrollidinone 4.1 872-50-4

Toluene 6.1 108-88-3

Diisopropylamine 0.9 108-18-9



Stage-I 1.00 -



Benzoic acid 0.5 65-85-0


DM water 0.9 7732-18-5

63 Apremilast


Dimethyl Sulphone 0.6 67-71-0

N-butyl lithium (2.5 m in hexane) 3.7 109-72-8

Hexamethyldisilazane 1.2 999-97-3

3-ethoxy-4-methoxy Benzaldehyde 1.0 1131-52-8

Boron trifluoride diethyl etherate 1.6 109-63-7




P-toluene Sulphonic acid monohydrate 1.1 6192-52-5

Methanol 5.4 67-56-1

Palladium carbon 0.1 7440-05-3



L-pyro glutamic acid 0.2 98-79-3


Glacial Acetic acid 3.2 64-19-7

Stage-I 1.00 -

3-Acetamido Phthalic anhydride 0.8 6296-53-3





Acetyl chloride 0.2 75-36-5

33


Benzyl alcohol 1.2 100-51-6

Methanol 15.0 67-56-1


Methanol 21.0 67-56-1

Benzyl alcohol 0.6 100-51-6

Stage-II 1.0 -

Dm water 1.00 7732-18-5

64 Brexpiprazole

O-Xylene 15.0 95-47-6

Sodium Tert Butoxide 1.6 865-48-5

4-bromo Benzo[b] thiophene 1.0 5118-13-8

Racemic BINAP 0.03 98327-87-8

10% Palladium Charcoal 0.04 7440-05-3

Piperazine anhydrous 1.6 110-85-0



Stage-I 1.00 -

Dimethyl sulfoxide 4.4 67-68-5


7-(4-chlorobutoxy)-1H-quinolin-2-one 0.76 913613-82-8


Methanol 17.8 67-56-1


Acetone 26.50 67-64-1

p-Toluene Sulphonic acid monohydrate 0.5263 6192-52

Stage-II 1.00 -

Methanol 13.8 67-56-1

Conc. HCl 0.24 7647-01-0

DM water 9.5 7732-18-5

Tert butyl amine 0.43 75-64-9

65 Duloxetine Hydrochloride


S-alcohol 1.0 64-17-5


Potassium iodide 0.09 7681-11-0

1-Fluronapthalen 0.72 321-38-0




Oxalic acid Dihydrate 0.72 6153-56-6


Stage-I 1.0 -

Toluene 11.1 108-88-3




Phenyl Chloro formate 0.468 1885-14-9



Acetone 7.0 67-64-1

Ethyl acetate.HCl 0.8 7647-01-0

DM Water 10.7 7732-18-5

Stage-II 1.0 -

34




Acetone 8.6 67-64-1

Ethyl acetate.HCL 1.3 7647-01-0

66 Empagliflozin


KSM-I ((5-bromo-2-chlorophenyl)(4-flurophenyl) methanone) 1.0 -

KSM-II ((3S)-tetrahydrofuran-3-ol) 0.3 -





Stage-I 1.00 -


Borontrifluoride etherate 0.6 109-63-7



Methylene chloride 8.0 75-09-2


Seeding 0.01 -


Stage-II 1.0 -

n-Butyl lithium 1.50 109-72-8

TMS – Gluconolactone 0.0 32384-65-9


Trifluoro acetic acid 0.6 76-05-1





MTBE 1.50 1634-04-4

n-Heptane 1.4 142-82-5



BF3 etherate 0.8196 -



67 Lamotrigine



Amino guanidine bicarbonate 1.03 2582-30-1

2, 3-Dichloro benzoyl nitrile 1.0 77668 – 42 – 9



n-Propanol 16.55 71-23-8

Stage-I 1.0 -


68 Linagliptin


Diisopropylethylamine 0.58 7087-68-5

Bromo-3-methyl xanthine 1.0 93703-24-3

1-bromo-2-butyne 0.6 3355-28-0


35


N-methyl pyrollidinone 4.0 872-50-4

Linagliptine Stage-I 1.0 -

KSM-III 0.775 -


IPA 7.0 67-63-0



Methanol 2.37 67-56-1

MDC 2.37 75-09-2

DMF 3.0 68-12-2

Linagliptine stage-II 1.0 -

3-(R)-Boc-aminopiperidine 0.53 309956-78-3



MDC 23.0 75-09-2

Trifluoroacetic acid 3.77 76-05-1

Caustic 2.31 1310-73


Ethanol 5.6 64-17-5


Stage-III 1.0 -


Mandelic acid 0.34 611-72-3

DM water 55.13 7732-18-5

Sodium hydroxide 0.1014 1310-73

69 Lurasidone Hydrochloride

Methylene Chloride 10.6 75-09-2

(1R,2R)-1,2-cyclohexanedimethanol 1.0 65376-05-8


Methane sulfonyl chloride 0.16 124-63-0




3-(1-Piperazinyl)-1,2- bezothiazole 0.7 87691-87-0

Stage-I 1.0 -


tetra butyl ammonium hydrogen sulphate 0.057 32503-27-8


Toluene 14.5 108-88-3

Stage-II 1.0 -

(3aR,4S,7R,7aS),-4,7-methano-1H-isoindole-1,3(2H)-dione 0.4 14805-29-9


18-crown ether 0.03 17455-13-9

Process water 6 7732-18-5


Denatured alcohol 15.8 64-17-5


Conc.HCl 0.25 7647-01-0

Stage-III 1.00 -

DM water 14 7732-18-5

70 Macitentan


5-4-bromophenyl)-4,6-dichloropyrimidine 1.0 146533-41-7

36

N-propyl Sulfuric diamide 4.9 147962-41-2



Citric acid monohydrate 2.2 5949-29-1


Mono ethyl glycol 7.9 107-21-1

Stage-i 1.00 -




N-butyl acetate 5.7 123-86-4


Stage-ii 1.0 -

5-bromo-2-chloropyrimidine 0.7 32779-36-5



Dm water 22.0 7732-18-5




71 Pregabalin


R-CMH 1.0 181289-15-6


Liq Bromine 0.896 7726-95-6


Conc. HCl 2.1 7647-01-0


Stage-I 1.0 -

DM Water 4.0 7732-18-5

72 Riociguat

Dimethyl Formamide 14.27 68-12-2

N,N-Diisopropylethylamine 0.63 7087-68-5

Benzeneazomalono nitrile 0.67 -

Raney Nickel 0.35 12003-78-0




Methyl chloroformate 0.64 79-22-1

1-(2-Fluorobenzyl)-1H-pyrazolo [3,4-b ]pyridine-3-

carboximidamide Hydrochloride 1.0

256499-19-1

Pyridine 0.24 110-86-1


Riociguat stage-I 1.0 625115-55-1


L N, N-Dimethyl formamide 0.85 68-12-2

Methyl iodide 0.03 74-88-4

N, N-Dimethyl formamide 0.10 68-12-2

Cesium carbonate 0.1015 534-17-8


Hyflo 2.0 61790-53-2



Maleic acid 0.241 110-16-7

37

Stage-II 1.0 -

Methanol 12.9 67-56-1


Ammonia 0.4389 7664-41-7

DM Water 17.05 7732-18-5

Riociguat AL polymorph 0.205 625115-55-1

Sodium Hydroxide Flakes 0.205 1310-73-2

73 Sofosbuvir

MDC 12.0 75-09-2

Al L-anine isopropyl esterdrorochloride 0.87 62062-65-1

Phenyl Dichlorophosphate 1.0 770-12-7

TEA 1.25 121-44-8


2, 3, 4, 5, 6-pentafluoro 0.97 1003050-32-5

Phenol 0.91 108-95-2

DIPE 4.7 108-20-3

Light liquid paraffin 2.5 8012-95-1



Deoxy-2-fluoro-2’-methyluridine 0.44 863329-66-2

Sofosbuvir Stage-I 1.0 1190307-88-0


Tert-Butyl magnesium Chloride 1.8 677-22-5

Ammonium chloride 0.32 12125-02-9



Citric acid 0.48 77-92-9

MDC 21.1 75-09-2

DIPE 2 108-20-3

Methanol 2.25 67-56-1

Sofosbuvir Stage-II 1.0 1190307-88-0


n-heptane 7.53 142-82-5

74 Teriflunomide

Cyano acetic acid 0.62 372-09-8

Phos phorous Pentachloride 1.5 10026-13-8


4-Trifluoromethyl aniline 1.0 455-14-1





Dimethylformamide 5.0 68-12-2


Teriflunomide Stage-I 1.0 108605-62-5

Isopropenyl acetate 0.7 108-22-5






Teriflunomide stage-II 1.0 108605-62-5

75 Vardenafil HCl Trihydrate

Chloro sulphonic acid 2.0 7790-94-5

38

Thionyl chloride 0.5 7719-09-7

KSM 1.0 -



Reaction Mass-I 5.5 -


Acetone 10.0 67-64-1


Conc. HCl 0.2401 7647-01-0

Acetone 2.77 67-64-1

Stage-III 1.0 -

Purified Water 0.23 7732-18-5

76 Ivacaftor


Diethyl (ethoxymethylene) propanedioate 1.0 87-13-8

Aniline 0.5 62-53-3


Sulfolane 3.8 126-33-0

Stage-I 1.00 -

Polyphosphoric acid 4.00 8017-16-1

Methanol 3.96 67-56-1


O-Phosphoric acid 8.3 7664-38-2



Stage-II 1.00 -

N,N’-Dicyclohexylcar bodiimide 1.85 538-75-0

5-Amino-2, 4-di-tert-butyl phenol 1.3 873055-58-4


Ethanol 11.8 64-17-5

Water 41.3 7732-18-5

Isopropyl Acetate 11.3 108-21-4

Stage-III 1.0 -

77 Nabumetone

Acetone 25.425 67-64-1


Candesartan Cilexetil-I 1.833 145040-37-5

Candesartan Cilexetil-II 2.200 145040-37-5


Cyclohexyl 1-Chloro Ethyl Carbonate 0.672 99464-83-2

D M Water 92.414 7732-18-5


Dimethyl-Formamide 3.153 4472-41-7

Ethyl Alcohol 1.041 64-17-5


Hyflow 0.060 61790-53-2

Methanol 8.800 67-56-1



Triethyl Amine 3.163 121-44-8

78 Nitazoxanide

Ethyl Alcohol 0.600 64-17-5

Formamidaceate 1.611 91-56-5

Hydrogen gas 1.831 1333-74-0

39

KSM-I 1.299 -

KSM-II 1.260 -

KSM-III 0.647 -

Pd/c 0.141 7440-05-3

POCI3 1.999 10025-87-3


Stage I 1.831 -

Stage II 1.886 -

Stage III 1.471 -

Stage IV 1.000 -

79 Lansoprazole

4-Methoxy-3-hydroxy Acetophenone 0.549 6100-74-9

1-Bromo-3-Chloropropane 1.044 109-70-6

6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride 0.756 84163-13-3

Iloperidone 1.000 133454-47-4

Methanol 0.500 67-56-1



Sodium Bromide 0.303 7647-15-6

Stage I 0.714 -

80 Entacapone

Hydrochloric Acid 0.953 764701-0

KSM-I 1.985 -

KSM-II 1.489 -


Sodium Hydroxide 0.376 1310-73


Stage I 1.886 -

Stage II 1.471 -

81 Daclatasvir

3-Morpholino-1-(4-(2-oxopiperidin-1-yl)phenyl)5,6-

dihydropyridin-2(1H)-one

1.935 545445-44-1

4-Methoxy phenyl hydrazine hydrochloride 0.798 19501-58-7

Ammonia Solution 2.427 1336-21-6


Ethyl Oxalyl chloride 0.832 4755-77-5

Ethylene glycol 18.204 107-21-1

MDC 42.355 75-09-2

Methanol 25.747 67-56-1

Pyridine 0.522 110-86-1

Stage I 1.117 -

Stage I A 1.210 -

Stage II 1.311 -

Sulphuric acid 0.580 7664-93

82 Elvitegravir

5-Bromo-2-chloro-4-ethoxy Diphenyl methane 2.453 461432-23-5

4-Dimethylaminopyridine 0.029 1122-58-3



Borontrifluoride dfietherate 1.540 109-63-7

Delta gluconolactone 0.579 90-80-2


Methanol 9.813 67-56-1

N-methyl Morpholine 2.629 109-02-4

40

Pyridine 3.039 110-86-1

Stage I 1.207 -

Stage I A 1.089 -

Stage II 0.873 -

THF 30.503 109-99-9


83 Sacubitril Calcium

(2R,4S)-5-biphenyl-4-yl-4-tert-butoxy carbonyl amino-2-methyl

pentanoic acid (Adv. Int.) 1.14

1012341-50-2

Ethanol (KSM) 3.41 64-17-5



Succinic anhydride (KSM) 0.35 108-30-5



Sodium Hydroxide 0.13 1310-73

Calcium chloride monohydrate 0.31 22691-02-7

Isopropyl acetate 3.33 108-21-4

Water 25.71 7732-18-5

84 Tenofovir

Adenine 0.22 73-24-5

DMF 0.56 68-12-2

R-(propylene carbonate 4.9 16606-55-6


Toluene 23.2 108-88-3


Mg tert Butoxide 6.3 32149-57-8

p-toluene sulfonyloxy methyl phosphonate 7.9 31618-90-3

Bromo tri methyl silane 1.00 2857-97-8


Phenol 27.7 108-95-2

1-methyl-2pyrrolidone 1.0 872-50-4


Dicyclohexyl carbodiimide 15.1 538-75-0





L-alanine isopropyl ester 22.0 62062-65-1

Sodium dihydrogen phosphate 30.8 7558-80-7

Sodium sulfate 9.9 7757-82-6

Acetone 1.0 67-64-1

Fumaric acid 1.3 110-17-8

85 Lumacaftor

(S)-4-(4-Amino Benzyl)-1,3-Oxazolidin 2-One 1.754 152305-23-2

(S)-4-(4-Hydrazinyl Benzyl)-1,3-Oxazolidin 2-One 1.891 139264-57-6

4-Dimethylamino Butanol Diethyl Acetate 1.728 1116-77-4



Sodium Sulphite 0.460 7757-83-7

86 Ledipasvir


DIPEA 0.546 7087-68-5

KSM 0.683 1401991-17-0

41

KRM-I 0.828 -

KRM-II 0.255 -

KRM-III 0.253 -

Methanol 12.407 67-56-1

NaB(OAC)3 0.450 56553-60-7

Pd(II)acetate 0.034 3375-31-3


PTSA.H2O 1.556 -


Stage I 1.373 -

Stage II PTSQA 0.872 -

THF 15.625 109-99-9

Toluene 2.732 108-88-3

87 Deferasirox

2,3 Dichloro Benzaldehyde 0.667 6334-18-5

2,3 Dichlorobenzylidine Methylacetoacetate 1.000 74073-22-6

3-Amino Crotonic acid Ethyl ester 0.630 626-34-6

Methyl Aceto Acetate 0.465 105-45-3

42

ANNEXURE – II

PLANT LAYOUT

EXISTING

43

PROPOSED

44

ANNEXURE – III

BRIEF MANUFACTURING PROCESS

1. CANDESARTAN CILEXETIL

Manufacturing Process

Stage – I:

Methyl 2-[({2’-cyanobiphenyl-4-yl} methyl) amino]-3-nitrobenzoate reacts with stannous

chloride in presence of ethyl acetate then reaction mass obtained by hydrolysis.

Stage – II:

Charge stage-I in toluene reacts with Tetra ethyl ortho carbonate in presence of acetic acid.

Stage – III:

Sodium azide reacts with Tri n butyl tin chloride in o-Xylene then separation and hydrolysis.

Charge in acetone reacts with Triethyl amine the centrifugation of reaction mass. Charge in

Dimethyl Formamide reacts with Potassium carbonate & Cyclohexyl 1-chloro ethyl

carbonate then reaction mass goes in to acetone. Charge in Dichloromethane react with

sodium bicarbonate & then add methanolic hydrochloric acid then separate and add in

ethanol for reaction mass centrifugation. Candesartan Cilexetil crude is purified with

mixture of Acetone and D M Water to get for purification for Candesartan Cilexetil pure.

45

NO2

COOH

COOH

3-Nitro phalic acid

METHANOLD.M.WATERCONC.SULPHUIRIC ACID

D.M.WATER

CONC.SULPHURIC ACID

COOH

NO2

COOCH3

METHYL 2-CARBOXY 3-NITROBENZOATE

Thionyl chlorideTolueneDimethylformamideSodium azidet-ButanolSodium bicarbonateD.M.Water

Methanol

Sodium chlorideNitrogenSO2HCl

COOCH3

NO2

NH-CO-O-C(CH3)3

Methyl 2-t-butoxycarbonylamino-3-nitrobenzoate

4-(2-cynophenyl)benzyl bromidePotassium carbonatePotassium iodideAcetonitrileConc. HClSodium bicarbonateD.M. waterMethanol

Potassium Bromidet-ButanolPotassium carbonatePotassium iodide

Chemical Reaction

46

NO2

COOCH3

NH

CN

Etyl acetateConc. HClTin chloride dihydrateSodium HydroxideD.M. watermethanol

Sodium chlorideD.M. waterNa2SnO3H2SnO3

CN

NH

COOCH3

NH2

Tetra ethyl ortho carbonateTolueneAcetic acid

EthanolAcetic acid

N

N

COOCH3

CN

OCH3

Methyl 1[(2'-cyanobiphenyl-4yl)methyl]-2-ethoxy-benzimidazole-7-carboxylate

47

CH3O

N

NN

N

N

N

C(Ph)3

COOO

O

CH3

O

1-(Cyclohexaloxycarbonyloxy)ethyl-2-ethoxy-1[2'-{N-tri phenyl methyl tetrazole-5-ylbiphenyl-4-yl)-methyl] benzimidazole-7-carboxylate

Conc.HClMethanolDichloromethaneSodium bicarbonateD.M.WaterEthanolCyclohexaneD.M. waterAceton

TritanolCO2Sodium chloride

O

CH3

OO

O

CO

N

N

N

NN

N

OCH3

H

Canadesatan Cilexitil

CH3O

N

NN

N

COOCH3

N

N

O-xyleneTri butyl tin chlorideSodium azideD.M. waterSodium hydroxideConc. HCl

Sodium chlorideTri butyl tin hydroxideMethanol

2-Ethoxy-1[2'-{1h-tetrazole-5-yl}biphenyl-4yl)-methyl]benzimidazole-7carboxylic acid

C(Ph)3

N

N

COOCH3

N

NN

N

OCH3

H

DichloromethaneTrityl phenyl chlorideTriethyl amineAcetonitrile

Triethyl amine hydrochloride

2-Ethoxy-1[2'-{N-tri phenyl methyl tetrazole-5-yl}biphenyl-4yl)-methyl]benzimidazole-7carboxylic acid

Cyclohexyl 1-chloroethyl carbonatePotassium carbonatePotassium iodideDimethyl sulphoxideAcetonitrileD.M. water

Potassium chlorideCO2Potassium carbonatePotassium iodide

48

Material Balance

Stage – 1

Total input

Kgs. Starting Material

Product output

Candesartan Cilexetil-I

Quantity

Kgs. Output details

1.30 EBC-III 1.0 Kg

1.0 Product

6.55 Acetone 5.46 Acetone Recovery

13.51 D M Water 1.09 Acetone Recovery Loss

1.32 Triethyl Amine 0.09 Evaporation Loss

15.05 Aqueous Effluent

22.69 Total 22.69 Total

Stage-2

Per Kg

Product Starting Material

Product output

Candesartan Cilexetil - II

Per Kg

Product Output details

1.98 Dimethyl formamide

1.0 kg

10.17 MLR Aq DMF+ Byproducts +Salts (ETP)

1.00 Candesartan Cilexetil Stage-I 5.1 Acetone ML + product loss (sale)

0.24 Anhydrous Potassium Carbonate 2.9 Aq Acetone from cleaning (ETP)

0.36 Cyclohexyl 1-chloro ethyl

carbonate

0.02 Other Solid waste (ETP)

8.00 DM water 1.0 Product

4.70 Acetone

2.1 DM water for cleaning

0.8 Acetone for cleaning


Stage-3

Per Kg

Product Starting Material

Product output

Candesartan Cilexetil - III

Per Kg

Product Output details

28.30 Methylene dichloride

1.0 kg

16.52 Aq layer + Salt +Byproducts

2.13 Candesartan Cilexetil Stage-II 19.01 Aq Methanol + Salt +Byproducts

1.28 Conc. Hydrochloric acid 0.16 Hyflo

8.43 Methanol 10.70 Aq Acetone + By products

23.34 DM Water 28.30 Distilled MDC

1.15 Sodium Bicarbonate 10.90 MLR Alcohol+Cyclohexane

0.11 Hyflo 0.13 Vapor loss Aq Acetone

0.53 Sodium chloride 0.02 Other Solid waste

1.03 Denatured Alcohol 1.00 Product

8.95 Cyclohexane

7.93 Acetone

1.58 Acetone + Methanol cleaning

2.00 DM water for cleaning


49

2. CELECOXIB

Manufacturing Process

Stage-I

Charging of trifluoro acetic acid, cooling to 0-5°C, addition of absolute alcohol & sulphuric

acid followed by heating of reaction mixture to 65-70°C and then after

Stage-II

Charging of Toluene followed by charging of sodium methoxide then cooling of mixture upto

0-5°C then charging of ethyl trifluoro acetate(Stage-I).After completion of reaction pH

adjustment of reaction mixture by addition of 20% sulphuric acid solution, charging of DM

Water to the reaction mixture and then layer separation. Product extraction from aq. layer

by Toluene. Finally isolation of Stage-II by combining of organic layer and distill out Toluene.

Packing of Residue (Stage-II) after distillation of Toluene.

Charging of 12.5 % Aqueous Isopropyl alcohol followed by 4-Sulfamoyl phenyl hydrazine

hydrochloride and Stage-II Heating of reaction mixture up to 80-85°C.thus by reaction

between 4-Sulfamoyl phenyl hydrazine hydrochloride and Stage-II at 80-85°C in presence of

12.5% Aq. Isopropyl alcohol we obtain Crude Celecoxib (Stage-III). Charcoalization of

reaction mixture and filtration through Hyflo bed at 80-85°C,Charging of DM Water into the

filtrate followed by chilling of reaction mixture up to 0-5°C.Finally centrifugation , drying &

packing of the material .

Charging of 30% Aqueous Isopropyl alcohol followed by stage-III, dissolution at 80-85°C,

Charcoalization of the material. Filtration through hyflo bed in hot condition, chilling of

reaction mass to 0-5°C, centrifugation of the material. Finally material is to be dried under

vacuum followed by milling, sifting & finally packing of the material.

50

Stage-2: Preparation of 1- ( 4-methylphenyl) 4, 4, 4-trifluro butane 1, 3-dione

+ CF3COOC2H5CH3ONa

Toluene

CH3

COCH 2COCF 3

Mol. Wt. : 142. 08

Mol For.: C4H5F3O2CAS: 383- 63 - 1

Ethyltrifluoro acetate Stage-II ( 1, 3-Dione)

Mol.wt: 230

Mol For.: C11H9F3O2

Stage-3: Preparation of Celecoxib

Crude Celecoxib

Mol.wt: 381

Mol For.: C 17H14F3N3O2S

CAS: 169590- 42- 5

4-Methylacetophenone

Mol.wt: 134. 18

Mol For.: C9H10O

CH3

COCH3

Stage-1: Preparetion of Ethyl trifluroacetate

Absolute Alcohol

Conc. H2SO4

Trifluoroacetic acidMol. Wt. : 142. 08

Mol For.: C4H5F3O2CAS: 383- 63 - 1

Ethyltrifluoro acetate

CH3 O

CF3

O

SO2NH2

NHNH2 HCl

CH3

COCH2COCF3

+Aq. IPA

SO 2NH2

N

CF3

N

CH3

4-SPH-HCl 1, 3-Dione

Stage-IV: Purification of Celecoxib

Aq. IPA

Reflux

Reflux

Crude CelecoxibCelecoxib

F3C OH

O

CAS No: 122-00-9CAS No: 720-94-5

Mol Wt: 114. 02

Mol For: C2HF3O2

CAS No: 76-05-1

Mol Wt: 223. 5

Mol For: C6H10ClN3O2S

CAS No: 17852-52-7

Mol Wt: 230

Mol For: C11H9F3O2

CAS No: 720-94-5

SO2NH2

N

CF3

N

CH3

SO2NH2

N

CF3

N

CH3

Chemical Reaction

51

Material Balance

Stage – 1

form-1environmentclearance.nic.in/writereaddata/online/tor/02...2 appendix i (see paragraph - 6)...

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