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www.enaminestore.com
With development of on-line chemical directo-ries acquiring necessary reagents and building blocks for day-to-day research activity has be-come a technical routine. Many thousands of building blocks are now available in the market and sub-structure search can efficiently provide a selection of reagents to buy. However, this approach might be limited.
With over 100,000 building blocks synthesized and now available from our stock we are a re- cognized leader in the market. Our catalogue features versatile building block classes and adds 1,000 products each month. Although they all are available for purchase through www.enaminestore.com and many public or corporate chemical databases we wanted to gather together the most interesting and re-cently prepared building blocks to provide a series of useful guides to a novel and innova-tive chemistry.
Selected Building Block
Series
2 Fluorinated aliphatic amines
Fluorinated aliphatic amines
N
O
NN
Cl
Cl
F
F F
N
OCO2H
F
F
ClNH2N N
NC
F
O HN
N
N
N
NH
N
F F
MeO2C
MeON
N
OAc
HO CO2MeH
H
HNO2S
NN
F3C CF3
VinflunineLaboratoires Pierre Fabre, 1998
CitafloxacineDaiichi Sankyo Co., 2008
Nootropic agentMarck Research Laboratories, 2005
Antiurinary agentPfizer Inc., 2002
MelogliptinGlenmark Pharm., 2006
Motifs of fluorinated aliphatic amines are common in drug discovery.
3www.enaminestore.com
Linear amines
EN300-96615 EN300-114376
EN300-102325 EN300-74923
EN300-84693 EN300-35000
EN300-69309 EN300-32020
EN300-41781 EN300-93182
EN300-100456 EN300-94944
EN300-101814 EN300-93912
EN300-90872 EN300-40766
F
FH2NCF3
H2NO
H2N F F
F
SH2N
H2N FCF3H2N
O
F
F
H2NCF3H2N O
CF3H2NH2N
CF3
H2N
F H2NO
F3C
F
FH2N
F3CH2N
CF3H2N CF3
SH2N
HCl HCl
HCl
HCl
HCl
HCl HCl
HCl HCl
HCl HCl
4 Fluorinated aliphatic amines
NHN
N
O
HNNN
FO
CO2H
HNHN
NN
NN
NH2 HO
F3C OH
OF3C N
OOF3C
O
NO
F3CO
OHF3C NHBoc F3C NH2
94% 82%
70%
72%63%
F3C OEt
OO
F3C OEt
O
*HCl
F3C OEt
OOH
93%
94% 69%
NaBH4 P2O5
NaOH
Me3SOIEDC
MeNHOMe
t-BuOK
(PhO)2PON3 HCl
EN300-42754
Ciprofloxacin Nevirapine Abocavir
Recently we developed a practical synthesis of the novel building block: trans-2-(trifluoromethyl)-cyclopropanamine.1,2
Fragment of cyclopropanamine is common in approved drugs:
1. A. V. Bezdudny et al. Synthesis 2011, 1, 119.2. V. S. Yarmolchuk et al. Synthesis 2012, 44, 1152.
trans-2-(Trifluoromethyl)-cyclopropanamine
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Exocyclic amines
EN300-42754 EN300-104701
EN300-79761 EN300-112279
EN300-74868 EN300-75524
EN300-94391 EN300-27688
EN300-78062 EN300-26926
EN300-90484 EN300-27291
EN300-115151 EN300-96312
EN300-99908 EN300-109808
CF3
H2N
FF
H2N
F3C
H2N
FF
H2N
BocHN
FF
F3C
H2N
F3C
H2N
F3C
H2N
F
FH2N
CF3
H2N
F
FH2N CF3H2N
H2N
F F C3
H2N
FF
H2N
F
FH2N
HCl HCl
HCl
HCl
HCl
HCl
HCl
HCl HCl
6 Fluorinated aliphatic amines
N
N
NHO
FCl
NO
EN300-83298EN300-81684
NH
O
NH
O CF3
NH
O
CF3
Morpholine
NO F
N
OONHAc
NS
N N
O
O NHtBu
OH
S
N
O NO
NHCO2Et
Cl
O
NHN
O
Trifluoromethylated morpholines
Timolol Moricizine Moclobenide
Motif of morpholine is highly common in drug discovery. Many FDA-approved drugs contain morpholine moiety.
1. A. V. Shcherbatiuk et al. Tetrahedron 69 2013, 3796-3804.
Recently we developed a practical approach to trifluoromethylated mor-pholines. The trifluoromethyl substituent multidimensionally tuned the
metabolic stability, bacisity and lipophilicity of the parent structure.1
Geffitinib Linezolid
7www.enaminestore.com
Morpholines, Piperidines and Bicyclic amines
EN300-81684 EN300-97937
EN300-90726 EN300-79100
EN300-52620 EN300-73968
EN300-83298 EN300-113369
EN300-90738 EN300-109987
EN300-110108 EN300-100245
EN300-93067 EN300-73116
EN300-113083 EN300-73117
CF3O
NH
CF3
NH
CF3O
NH
CF3
NH
O
NH
F F
FFCF3HN
CF3NH
O
HN
F
CF3NH
O
HN
FF
HN
F
F
F
F
HN
CF3HNNHN
F
HN
FF
NHN
F
F
HCl HCl
HCl
HCl
HCl HCl
HCl
HCl HCl
2HCl
HCl 2HCl
8 Fluorinated aliphatic amines
Azetidines and Pyrrolidines
EN300-89727 EN300-100104
EN300-110434 EN300-89584
EN300-94689 EN300-89757
EN300-108152 EN300-102456
EN300-107382 EN300-109585
EN300-116702 EN300-73354
EN300-90481 EN300-79916
EN300-105150 EN300-95926
HN F HNF
F
HN
F
FNH F
F
CF3HN
NH
F
CF3
HNOH
NH
F
F
CF3
HN
NH
F
F
CO2Me
HN F
CF3
NH
HNF
F
CF3
CF3
NH
CF3HN
OH
CF3CF3
NH
HCl
HCl
HCl HCl
HCl HCl
HCl HCl
HCl HCl
HCl
HCl HCl
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Amino alcohols
EN300-51459 EN300-108152
EN300-29780 EN300-105150
EN300-84068 EN300-89625
EN300-74756 EN300-102059
EN300-111534 EN300-71887
EN300-82765 EN300-80830
EN300-112237 EN300-58599
EN300-82572 EN300-110084
CF3
OH
H2N
CF3
HNOH
CF3
OH
H2N
CF3HN
OH
CF3HN
OH
BocNCF3
OH
CF3H2N
OH
BocN
CF3
OH
CF3
OHH2N
HO
HN
CF3
CF3
OHH2N
CF3
HN
HO
CF3
OHH2N HN
CF3
OH
OHH2N
F3C CF3
HN
OH
HCl HCl
HCl HCl
HCl
HCl
HCl HCl
HCl
HCl
HCl
10 Fluorinated aliphatic amines
NH2
CF3
CO2H
NH2
CO2H
NH2
CO2H
NH2
CO2H
Cl
Cl
Cl
ClBrBr
MeLi CF3I
NCF3
CN
Ph
ICF3
CF3
O
H
CF3
OH
OMe
CF3NH
Ph
CNOH CF3
NH
Ph
CNOH
Pb(OAc)4
NH2
CF3
CO2H
Me3SiCN
NaOH, CHBr3
pinacole70%
1) t-BuLi2) HCOOMe
62%
++
HCl
(2 steps)90%
(2 steps)
R-phenylglycinol
(2 steps)95%
CF3-Bpg, EN300-53088
19F NMR label for peptide studies
1 P. K. Mikhailiuk et al. Angew. Chem. Int. Ed. 2006, 45, 5659.2 P. K. Mykhailiuk et al. Fluorine Chem. 2010, 131, 217.3 V. S. Kubyshkin et al. in Fluorine in Pharmaceutical and Medicinal Chemistry: From Biophysical Aspects to
Clinical Applications. (Eds.: V. Gouverneur, K. Muller), Imperial College Press, London, 2012, 91.4 M. Salwiczek et al. Amino Acids 2010, 39, 1589.
Amino acid CF3-Bpg was already used to study the structure of several
membrane-active peptides:3 gramicidin S, PGLa, SAP, (KIGAKI)3, Magainin
2, Temporin A and to evaluate the coil-coiled interactions within a poly-peptide sequence.4
Fluorinated amino acid 3-(trifluoromethyl)bicyclopent-[1.1.1]-1-ylg-lycine, (CF
3-Bpg), was designed,1 synthesized1,2 and validated1 as a
19F NMR label for structure analysis of membrane active peptides. The amino acid is perfectly suited to replace the residues of Val, Ile and Leu in peptides.
Val Leu lle CF3-Bpg
natural amino acide 19F-NMR label
Synthesis:
11www.enaminestore.com
Amino acids
EN300-65367 EN300-96908
EN300-101571 EN300-89429
EN300-53088 EN300-61407
EN300-89327 EN300-76959
EN300-110322 EN300-109585
EN300-75802 EN300-74301
EN300-34890 EN300-74493
EN300-85544 EN300-07164
NH2 F
FHO C2
NH
F
CO2H
CF3
NH2
HO C2
NBoc
FCO2H
NH2
F3C
CO2HCF3
NH
CO2H
F3CNHFmoc
CO2H
NBoc
CF3HO C2
NH
F
F
CO2H
NH
F
F
CO2Me
NH
CF3HO C2
F3C
H2NCO2H
NH
F3C
S
CO2H
F3C
H2NCO2H
F
NH2
F
CO2H
CF3
H2NCO2H
HCl
HCl
HCl
HCl HCl
HCl HCl
HCl
HCl HCl
12 Fluorinated aliphatic amines
Diverse derivatives
EN300-93520 EN300-109961
EN300-97552 EN300-74445
EN300-116549 EN300-78514
EN300-50504 EN300-30697
EN300-40849 EN300-90523
EN300-58944 EN300-78403
EN300-67015 EN300-29977
EN300-84859 EN300-35893
OF3C
H2NCF3
H2N
H2N
F3C
O
O
H2N
CF3
NH2
H2N
CF3
NH2
CF3
NHHN
CF3
H2N
Ph
F3C
OH
H2N
CF3
OH
H2N
Ph
CF3NH
O
CF3N
Ph
CO2H
CF3NH
O
NH2
F
F
CO2HCF3
NH
O
NH2
F
F
CO2HF3C
NH
O
HCl 2HCl
2HCl
HCl 2HCl
HCl
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New Arrivals
EN300-124674 EN300-127532
EN300-156761 EN300-156956
EN300-137256 EN300-129123
EN300-123357 EN300-142149
EN300-157667 EN300-157661
EN300-160286 EN300-137379
EN300-155382 EN300-126976
EN300-126061 EN300-127298
N
F
HNH
F
N
O F
F
HNH
O F
F
N
F
H
CF3
NH
NH
F CF3
NH
CF3
NH
NH
O
CF3
NH
F
F
NH
F
NH
OF
F
NH
F FF
F
F
F
CF3
N
NH2
NH
F
HCl HCl
HCl HCl
HCl
HCl HCl
HCl
HCl HCl
HCl HCl
HCl HCl
14 Fluorinated aliphatic amines
New Arrivals
EN300-141346 EN300-142130
EN300-142012 EN300-153048
EN300-171143 EN300-128644
EN300-171045 EN300-159776
EN300-157446 EN300-155850
EN300-172096 EN300-171923
EN300-130197 EN300-173310
EN300-132383 EN300-131174
FNH2
CF3
NH2
OH
NH2
F
BocNH NH2
F F
CF3
NH2 CF3
NH2
CO2H
CF3 NH2
O NHBoc
NH
F
CF3
NH2
NH
OH
F
F
F
F
O NH2 NH
F F
OH
CF3
O
NH2
NH
F
FOH
FF
NH2
NH
OH
CF3
HCl HCl
HCl
HCl
HCl HCl
HCl HCl
15www.enaminestore.com
Notes
16 Fluorinated aliphatic amines
Notes
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