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S1

Electronic Supplementary Information

One-pot Palladium catalyzed ligand and metal oxidant-free aerobic oxidative isocyanide insertion

leading to 2-amino-substituted-4(3H)-quinazolinones

Shinde Vidyacharan, N. C. Chaitra, A. Sagar and Duddu S. Sharada*

Department of Chemistry, Indian Institute of Technology (IIT) Hyderabad, Ordnance Factory Estate

Campus, Yeddumailaram – 502 205, Medak District, Telangana, India.

Table of Contents

Experimental section……………………………………………………………… (S2)

General procedure for the synthesis of 2-amino-substituted-4(3H)-quinazolinones.. (S2)

Spectral data of all compounds (5a-5s)…………….…………………………… (S3-S8)

Copies of 1H,

13C NMR spectra of all compounds (5a-5s)……………………… (S9-S28)

References…………………………………………………………………………………… (S28)

S2

Experimental Section

General: IR spectra were recorded on a Bruker Tensor 37 (FTIR) spectrophotometer. 1H NMR spectra

were recorded on Bruker Avance 400 (400 MHz) spectrometer at 295 K in CDCl3; chemical shifts (δ in

ppm) and coupling constants (J in Hz) are reported in standard fashion with reference to either internal

standard tetramethylsilane (TMS) (δH = 0.00 ppm) or CHCl3 (δH = 7.25 ppm). 13

C NMR spectra were

recorded on Bruker Avance 400 (100 MHz) spectrometer at RT in CDCl3; chemical shifts (δ in ppm) are

reported relative to CHCl3 (δC = 77.00 ppm). In the 1H-NMR, the following abbreviations are used

throughout: s = singlet, d = doublet, t = triplet, q = quartet, qui = quintet, m = multiplet and br s = broad

singlet, sept = septet. The assignment of signals were confirmed by 1H and

13C spectral data. High-

resolution mass spectra (HR-MS) were recorded on an Agilent 6538 UHD Q-TOF using multimode

source. Microwave experiments were carried out with CEM Discover LabmateTM

instrument in 10 ml

vial, closed vessel, Power: 250W, Temperature: 60 °C-100 oC for 50-100 minutes. Melting points were

determined using melting point apparatus manufactured by GUNA enterprises, India and are uncorrected.

All small scale reactions were carried out using standard syringe-septum technique. Reactions were

monitored by TLC on silica gel using a combination of hexane and ethyl acetate as eluents. Solvents were

distilled prior to use.

General Procedure for the synthesis of 2-amino-substituted-4(3H)-quinazolinones (5a-5v):

In an oven dried schlenk tube under argon atmosphere, were added isatoic anhydride (1 equiv, 0.609

mmol), amine (1 equiv, 0.609 mmol) and activated 4Å molecular sieves (150 mg) followed by addition of

dry DMSO (2 mL). The reaction mixture was stirred at 110 oC for 30 min to 4 h. The completion of first

step was monitored by TLC. Once dinucleophile was formed Pd(OAc)2 (5 mol%), CyNC (1.5 equiv.,

0.913 mmol) were added in same pot under argon atmosphere. It was evacuated and filled with O2 by

using a balloon. The resulting reaction mixture was heated at 110 oC. Progress of the reaction was

monitored by TLC, which took 15-17 h. The reaction mixture was then quenched with water and the

product was extracted with ethyl acetate. The organic layer was dried over Na2SO4 and concentrated in

vacuo. The crude product was purified by column chromatography on silica gel using petroleum

ether/ethyl acetate as eluent, which afforded the desired product (5a-5w). All the compounds were

confirmed by FTIR, 1H NMR,

13C NMR and HR-MS Spectral analyses. Among 22 compounds,

19 are unknown and 3 (5a, 5i & 5m) are known.

S3

Spectral data of all compounds (5a-5s):

3-Benzyl-2-(cyclohexylamino)quinazolin-4(3H)-one (5a):[1]

White solid (75%), Mp 106-108 oC.

[TLC control Rf(1) = 0.30, Rf(5a) = 0.70 (petroleum ether/ethyl acetate 8:2, UV detection)]. IR (MIR-

ATR, 4000–600 cm-1

): ʋmax = 3324, 3059, 2921, 1627, 1584, 1517, 1487, 1384, 1230, 1198, 1029, 951,

751, 640.

1H NMR (CDCl3, 400 MHz): δH = 8.18 (dd, 1H, Ja = 8.1 and Jb = 1.2 Hz), 7.60-7.56 (m, 1H), 7.38-7.30

(m, 4H), 7.29-7.26 (m, 1H), 7.17 (t, 1H, J = 7.6 Hz), 5.32 (s, 2H), 4.36 (d, 1H, J = 6.8 Hz), 3.99-3.91 (m,

1H), 1.83 (dd, 2H, Ja = 8.6 and Jb = 3.7 Hz), 1.53-1.46 (m, 3H), 1.40-1.29 (m, 2H), 1.18-0.98 (m, 3H). 13

C

NMR (CDCl3, 100 MHz): δC = 163.2, 149.5, 149.2, 135.3, 134.4, 129.4, 128.2, 127.4, 126.6, 124.9, 122.4,

116.9, 49.7, 44.6, 42.5, 25.6, 24.2.

HR-MS (ESI+) m/z calculated for [C21H24N3O]+ = [M+H]

+: 334.1914; found: 334.1901.

2-(Cyclohexylamino)-3-(4-methoxybenzyl)quinazolin-4(3H)-one (5b): White solid (78%), Mp 130-132 oC. [TLC control Rf(1) = 0.30, Rf(5b) = 0.80 (petroleum ether/ethyl acetate 8:2, UV detection)].

IR (MIR-ATR, 4000–600 cm-1

): ʋmax = 3421, 2999, 2928, 2852, 1662, 1610, 1578, 1561, 1475, 1450,

1346, 1247, 1176, 1033, 982, 765, 693.

1H NMR (CDCl3, 400 MHz): δH = 8.18 (dd, 1H, Ja = 7.8 and Jb = 1 Hz ), 7.60-7.56 (m, 1H), 7.37 (d, 1H,

J = 8.3 Hz), 7.21 (d, 2H, J = 8.8 Hz), 7.17 (m, 1H), 6.88 (d, 2H, J = 8.3 Hz), 5.26 (s, 2H), 4.44 (d, 1H, J =

6.8 Hz), 3.99-3.93 (m, 1H), 3.79 (s, 3H), 1.88-1.86 (dd, 2H, Ja = 8.1 and Jb = 3.7 Hz ), 1.54-1.52 (m, 3H),

1.41-1.32 (m, 2H), 1.20-1.15 (m, 1H), 1.10-1.01 (m, 2H). 13

C NMR (CDCl3, 100 MHz): δC = 163.4,

159.7, 149.4, 149.3, 134.3, 127.9, 127.3, 127.2, 124.9, 122.3, 116.9, 114.7, 55.3, 49.7, 44.1, 32.6, 25.6,

24.3.

HR-MS (ESI+) m/z calculated for [C22H26N3O2]+ = [M+H]

+: 364.2020; found: 364.2003.

2-(Cyclohexylamino)-3-(4-methylbenzyl)quinazolin-4(3H)-one (5c): White solid (78%), Mp 138–140 oC. [TLC control Rf(1) = 0.30, Rf(5c) = 0.70 (petroleum ether/ethyl acetate 8:2, UV detection)].

IR (MIR-ATR, 4000–600 cm-1

): ʋmax = 3422, 2926, 2853, 1659, 1562, 1475, 1346, 1224, 1147, 1069, 986,

765, 695. 1H NMR (CDCl3, 400 MHz): δH = 8.18 (dd, 1H, J = 7.8 Hz), 7.59-7.55 (m, 1H), 7.37 (d, 1H, J =

8.3 Hz), 7.18-7.16 (m, 5H), 5.28 (s, 2H), 4.4 (d, 1H, J = 6.8 Hz), 3.90-3.99 (m, 1H), 2.33 (s, 3H), 1.80-

1.87 (m, 2H), 1.50 (d, 3H, J = 10.3 Hz), 1.30-1.41 (m, 2H), 1.12-1.19 (m, 1H), 0.99-1.08 (m, 1H).13

C

NMR (CDCl3, 100 MHz): δC = 163.2, 149.5, 149.3, 138.0, 134.3, 132.21, 130.0, 127.3, 126.6, 124.9,

122.4, 116.9, 49.8, 44.4, 32.5, 25.6, 24.2, 21.1.


+: 348.2070; found: 348.2056.

2-(Cyclohexylamino)-3-(3,4-dimethoxybenzyl)quinazolin-4(3H)-one (5d) : Orange solid (75%), Mp

100-102 oC. [TLC control Rf(1) = 0.30, Rf(5d) = 0.60 (petroleum ether/ethyl acetate 8:2, UV detection)].

S4

IR (MIR-ATR, 4000–600 cm-1

): ʋmax = 3413, 2928, 2853, 1667, 1580, 1475, 1380, 1260, 1141, 1027,

766, 694.

1H NMR (CDCl3, 400 MHz): δH = 8.17 (dd, 1H, Ja = 7.8 and Jb = 1 Hz), 7.59-7.55 (m, 1H), 7.36 (d, 1H,

J = 8.3 Hz), 7.16 (t, 1H, J = 7.6 Hz), 6.82-6.78 (m, 3H), 5.24 (s, 1H), 4.51 (d, 1H, J = 7.3 Hz), 3.95 (dt,

1H, Ja = 6.6 and Jb = 3.1 Hz), 3.86 (s, 3H), 3.81 (s, 3H), 1.88-1.85 (m, 2H), 1.53 (d, 3H, J = 8.3 Hz),

1.37-1.31 (m, 3H), 1.14-1.10 (m, 3H). 13

C NMR (CDCl3, 100 MHz): δC = 163.2, 149.9, 149.5, 149.4,

149.0, 134.3, 127.8, 127.3, 124.9, 122.4, 119.0, 116.9, 109.7, 56.0, 55.9, 49.8, 44.6, 32.6, 25.6, 24.8.

HR-MS (ESI+) m/z calculated for [C23H28N3O3]+ = [M+H]

+: 394.2125; found: 394.2129.

2-(Cyclohexylamino)-3-(3-methoxybenzyl)quinazolin-4(3H)-one (5e): White solid (65%), Mp 108–

110 oC. [TLC control Rf(1) = 0.30, Rf(5e) = 0.70 (petroleum ether/ethyl acetate 8:2, UV detection)].

IR (MIR-ATR, 4000–600 cm-1): ʋmax = 3423, 2969, 2853, 1662, 1579, 1563, 1476, 1347, 1261, 1147,

1049, 985, 766, 694.

1H NMR (CDCl3, 400 MHz): δH = 8.19 (dd, 1H, Ja = 7.8 and Jb = 1.0 Hz), 7.62-7.57 (m, 1H), 7.38 (d,

1H, J = 8.3 Hz), 7.31-7.27 (m, 1H), 7.18 (t, 1H, J = 7.1 Hz), 6.86 (dd, 2H, Ja = 7.1 and Jb = 4.2 Hz), 6.82

(s, 1H), 5.30 (s, 2H), 4.41 (d, 1H, J = 6.8 Hz), 3.97 (dd, 1H, Ja = 7.6 and Jb = 4.2 Hz), 3.78 (s, 3H), 1.86

(dd, 2H, Ja = 8.3 and Jb = 3.9 Hz), 1.55-1.49 (m, 3H), 1.42-1.33 (m, 2H), 1.21-1.15 (m, 1H), 1.10-1.02

(m, 2H). 13

C NMR (CDCl3, 100 MHz): δC = 163.1, 160.5, 149.4, 149.2, 136.9, 134.3, 130.4, 127.3, 124.9,

122.4, 118.9, 116.8, 113.78, 112.2, 55.3, 49.7, 44.6, 32.5, 25.5, 24.2.

HR-MS (ESI+) m/z calculated for [C22H26N3O2]+ = [M+H]+: 364.2020; found: 364.2003.

2-(Cyclohexylamino)-3-(4-fluorobenzyl)quinazolin-4(3H)-one (5f): White solid (68%), Mp 118-120 oC. [TLC control Rf(1) = 0.30, Rf(5f) = 0.60 (petroleum ether/ethyl acetate 8:2, UV detection)].

IR (MIR-ATR, 4000–600 cm-1

): ʋmax = 3435, 2930, 2854, 1659, 1557, 750, 663.

1H NMR (CDCl3, 400 MHz): δH = 8.17 (dd, 1H, Ja= 8.1 and Jb = 1.2 Hz), 7.61-7.57 (m, 1H), 7.38 (d, 1H,

J = 7.38 Hz), 7.20-7.16 (m, 1H), 7.06 (t, 2H, J = 8.6 Hz), 5.29 (s, 2H), 4.27 (d, 1H, J = 7.3 Hz), 4.00-3.94

(m, 1H), 1.90-1.86 (m, 2H), 1.52 (d, 3H, J = 10.3 Hz), 1.42-1.33 (m, 2H), 1.18-1.14 (m, 1H), 1.08-1.00

(m, 2H). 13C NMR (CDCl3, 100 MHz): δC = 163.7, 163.1, 161.3, 149.4, 148.9, 134.5, 131.1, 131.0, 128.4,

128.3, 127.3, 125.0, 122.5, 116.8, 116.4, 116.2, 49.8, 43.9, 32.6, 25.6, 24.3.

HR-MS (ESI+) m/z calculated for [C21H23FN3O]+ = [M+H]

+: 352.1820; found: 352.1804.

3-(2-Chlorobenzyl)-2-(cyclohexylamino)quinazolin-4(3H)-one (5g): White solid (72%), Mp 108-110 oC. [TLC control Rf(1) = 0.30, Rf(5g) = 0.70 (petroleum ether/ethyl acetate 8:2, UV detection)].

IR (MIR-ATR, 4000–600 cm-1

): ʋmax = 3386, 2927, 2854, 1656, 1558, 1472, 1344, 1215, 1065, 830, 755,

663.

1H NMR (CDCl3, 400 MHz): δH = 8.08-8.06 (m, 1H), 7.51-7.47 (m, 1H), 7.30 (dd, 2H, Ja= 16.9 and Jb =

8.1 Hz), 7.16-7.11 (m, 1H), 7.09-7.04 (m, 3H), 5.34 (s, 2H), 4.28 (d, 1H, J = 7.3 Hz), 3.89 (dtd, 1H, Ja =

10.1, Jb = 6.7 and Jc = 3.9 Hz), 1.82-1.78 (m, 2H), 1.47 (d, 3H, J = 8.8 Hz), 1.31-1.22 (m, 2H), 1.08-1.00

S5

(m, 3H). 13

C NMR (CDCl3, 100 MHz): δC = 163.2, 149.5, 148.5, 134.5, 132.6, 132.4, 129.6, 129.4, 128.2,

127.9, 127.3, 125.0, 122.4, 116.7, 50.1, 41.1, 32.7, 25.6, 24.5.

HR-MS (ESI+) m/z calculated for [C21H23ClN3O]+ = [M+H]

+: 368.1524; found: 368.1509.

3-(2-(1H-indol-2-yl)ethyl)-2-(cyclohexylamino)quinazolin-4(3H)-one (5h): Yellow solid (62%), Mp

108-110 oC. [TLC control Rf(1) = 0.30, Rf(5h) = 0.50 (petroleum ether/ethyl acetate 8:2, UV detection)].

IR (MIR-ATR, 4000–600 cm-1

): ʋmax = 3381, 2928, 2853, 1653, 1562, 1349, 1248, 1147, 1011, 891, 741,

663.

1H NMR (CDCl3, 400 MHz): δH = 8.40 (br s, 1H), 8.02 (d, 1H, J = 8.3 Hz), 7.54 (d, 1H, J = 7.3 Hz), 7.43-

7.39 (m, 1H), 7.26 (d, 1H, J = 7.8 Hz), 7.18 (d, 1H, J = 8.3 Hz), 7.13-7.09 (m, 1H), 7.07-6.99 (m, 2H),

6.77 (s, 1H), 4.17 (t, 2H, J = 6.1 Hz), 3.61 (d, 1H, J = 7.3 Hz), 3.44-3.41 (m, 1H), 3.15 (t, 2H, J = 6.1 Hz),

1.44-1.33 (m, 6H), 1.16-0.99 (m, 3H), 0.80-0.74 (m, 1H). 13

C NMR (CDCl3, 100 MHz): δC = 163.3,

149.6, 149.3, 136.7, 134.2, 126.8, 126.6, 124.8, 123.2, 122.8, 120.2, 118.0, 117.1, 111.9, 111.8, 49.7,

43.5, 31.9, 25.5, 24.8, 24.1.


+: 387.2179; found: 387.2162.

3-Benzyl-2-(tert-butylamino)quinazolin-4(3H)-one (5i):[1]

White solid (40%), Mp 110–112 oC. [TLC

control Rf(1) = 0.30, Rf(5i) = 0.60 (petroleum ether/ethyl acetate 8:2, UV detection)].

IR (MIR-ATR, 4000–600 cm-1

): ʋmax = 3435, 3032, 2961, 2925, 1672, 1584, 1567, 1477, 1362, 1208,

1148, 976, 766, 695.

1H NMR (CDCl3, 400 MHz): δH = 8.18 (dd, 1H, Ja = 8.1 and Jb = 1.2 Hz), 7.58-7.56 (m, 1H), 7.38-7.31

(m, 4H), 7.26 (d, 2H, J = 7.3 Hz), 7.19-7.15 (m, 1H), 5.3 (s, 2H), 4.32 (s, 1H), 1.32 (s, 9H). 13

C NMR

(CDCl3, 100 MHz): δC = 163.3, 149.1, 148.4, 135.5, 134.2, 129.3, 128.2, 127.3, 126.7, 125.3, 122.4,

116.9, 52.6, 44.9, 28.8.


+: 308.1757; found: 308.1744.

2-(Tert-butylamino)-3-cyclohexylquinazolin-4(3H)-one (5j): White solid (32%), Mp 82–84 oC. [TLC

control Rf(1) = 0.30, Rf(5j) = 0.60 (petroleum ether/ethyl acetate 8:2, UV detection)].

IR (MIR-ATR, 4000–600 cm-1

): ʋmax = 3496, 2930, 2856, 1669, 1568, 1519, 1478, 1361, 1205, 1137,

953, 764, 697.

1H NMR (CDCl3, 400 MHz): δH = 8.07 (dd, 1H, Ja = 8.2 and Jb = 1.2Hz), 7.54-7.50 (m, 1H), 7.34-7.26

(m, 1H), 7.12-7.08 (m, 1H), 5.14 (br s, 1H), 4.6 (br s, 1H), 2.16-2.04 (m, 2H), 1.94-1.70 (m, 6H), 1.60-

1.42 (m, 2H). 13

C NMR (CDCl3, 100 MHz): δC = 163.5, 148.7, 148.3, 133.9, 127.1, 124.8, 122.1, 52.6,

30.4, 29.3, 26.6, 25.7.


+: 300.2070; found: 300.2057.

3-(2-Bromophenyl)-2-(cyclohexylamino)quinazolin-4(3H)-one (5k): White solid (48%), Mp 162-164 oC. [TLC control Rf(1) = 0.30, Rf(5k) = 0.50 (petroleum ether/ethyl acetate 8:2, UV detection)].

S6

IR (MIR-ATR, 4000–600 cm-1

): ʋmax = 3288, 2920, 2851, 1735, 1631, 1602, 1567, 1474, 1329, 1231,

1119, 1020, 957, 758, 648.

1H NMR (CDCl3, 400 MHz): δH = 8.13 (dd, 1H, Ja = 7.8 and Jb =1 Hz), 7.82 (dd, 1H, Ja = 8.1 and Jb = 1.2

Hz), 7.63-7.59 (m, 1H), 7.56-7.52 (m, 1H), 7.44-7.37 (m, 3H), 7.18-7.14 (m, 1H), 4.07-4.02 (m, 1H), 3.71

(d, 1H, J = 7.3Hz), 2.04-1.92 (m, 2H), 1.70-1.57 (m, 3H), 1.45-1.31 (m, 3H), 1.18-1.02 (m, 2H). 13

C

NMR (CDCl3, 100 MHz): δC = 162.0, 149.8, 147.9, 134.7, 134.5, 134.3, 131.4, 130.9, 129.5, 127.3, 125.0,

123.6, 122.4, 117.4, 49.8, 32.9, 32.8, 29.7, 28.8, 26.4, 25.6, 24.6, 24.5.

HR-MS (ESI+) m/z calculated for [C20H21BrN3O]+ = [M+H]

+: 398.0863; found: 398.0879.

2-(Cyclohexylamino)-3-phenylquinazolin-4(3H)-one (5l): White solid (35%), Mp 158–160 oC. [TLC

control Rf(1) = 0.30, Rf(5l) = 0.80 (petroleum ether/ethyl acetate 8:2, UV detection)].

IR (MIR-ATR, 4000–600 cm-1

): ʋmax = 3291, 2921, 2853, 1740, 1601, 1475, 1049, 759, 686.

1H NMR (CDCl3, 400 MHz): δH = 8.01 (dd, 1H, Ja = 8.1 and Jb =1.2 Hz), 7.69-7.58 (m, 2H), 7.42-7.23

(m, 2H), 7.14 (m, 1H), 4.90 (br s, 1H), 3.81 (m, 1H), 2.06 (dd, 1H, Ja = 12.2 and Jb = 2.9 Hz), 1.77-1.72

(m, 3H), 1.65-1.61 (m, 1H), 1.48-1.37 (m, 2H), 1.30-1.18 (m, 3H). 13

C NMR (CDCl3, 100 MHz): δC =

160.1, 150.6, 136.6, 128.7, 124.2, 123.4, 119.9, 113.2, 50.2, 32.9, 25.4, 24.6.


+: 320.1757; found: 320.1739.

3-Benzyl-6-chloro-2-(cyclohexylamino)quinazolin-4(3H)-one (5m):[1]

White solid (75%), Mp 124-126 oC. [TLC control Rf(1) = 0.30, Rf(5m) = 0.70 (petroleum ether/ethyl acetate 8:2, UV detection)].

IR (MIR-ATR, 4000–600 cm-1

): ʋmax = 3324, 3059, 2921, 1627, 1584, 1384, 1230, 1198, 1065, 951, 756,

640.

1H NMR (CDCl3, 400 MHz): δH = 8.13 (d, 1H, J = 2.4 HZ), 7.5 (dd, 1H, Ja = 8.8 and Jb = 2.4 Hz), 7.38-

7.24 (m, 6H), 5.3 (s, 1H), 4.39 (d, 1H, J = 7.3 Hz), 3.93-3.90 (m, 1H), 1.81 (dd, 2H, Ja = 8.6 and Jb = 3.7

Hz), 1.53-1.46 (m, 3H), 1.37-1.28 (m, 4H), 1.05-0.97 (m, 2H). 13

C NMR (CDCl3, 100 MHz): δC = 162.2,

149.3, 148.1, 135.0, 134.6, 129.5, 128.4, 127.6, 126.7, 126.6, 126.5, 117.7, 49.8, 44.7, 32.5, 29.7, 25.5,

24.2.


+: 368.1524; found: 365.1518.

6-chloro-2-(Cyclohexylamino)-3-(4-methoxybenzyl)quinazolin-4(3H)-one (5n): White solid (72%),

Mp 98-100 oC. [TLC control Rf(1) = 0.30, Rf(5n) = 0.70 (petroleum ether/ethyl acetate 8:2, UV

detection)].

IR (MIR-ATR, 4000–600 cm-1

): ʋmax = 3321, 3057, 2921, 1629, 1574, 1517, 1482, 1381, 1230, 1247,

1188, 1025, 951, 761, 643.

1H NMR (CDCl3, 400 MHz): δH = 8.12 (d, 1H, J = 2.4 Hz), 7.48 (dd, 1H, Ja = 8.8 and Jb = 2.4 Hz), 7.30-

7.26 (m, 1H), 7.19 (d, 2H, J = 8.3 Hz), 6.88 (d, 2H, J = 8.8 Hz), 5.22 (s, 2H), 4.47 (d, 1H, J = 6.8 Hz),

3.93-3.89 (m, 1H), 3.78 (s, 3H), 1.85 (dd, 2H, Ja = 8.3 and Jb = 3.9 Hz), 1.53-1.51 (m, 3H), 1.39-1.29 (m,

S7

3H), 1.08-0.99 (m, 2H). 13

C NMR (CDCl3, 100 MHz): δC = 162.2, 159.6, 149.4, 148.0, 134.6, 128.0,

127.8, 126.6, 126.5, 117.8, 114.8, 55.4, 49.9, 44.3, 32.6, 29.8, 25.5, 24.3.

HR-MS (ESI+) m/z calculated for [C22H25ClN3O2]+ = [M+H]

+: 398.1630; found: 398.1628.

6-Chloro-2-(Cyclohexylamino)-3-(4-methylbenzyl)quinazolin-4(3H)-one (5o): White solid (70%), Mp

136-138 oC. [TLC control Rf(1) = 0.30, Rf(5o) = 0.60 (petroleum ether/ethyl acetate 8:2, UV detection)].

IR (MIR-ATR, 4000–600 cm-1

): ʋmax = 3421, 2928, 2854, 16160, 1558, 1472, 1365, 1214, 1067, 896, 754,

663.

1H NMR (CDCl3, 400 MHz): δH = 8.13 (d, 1H, J = 2.4 Hz), 7.50-7.48 (m, 1H), 7.30-7.26 (m, 1H), 7.17-

7.12 (m, 5H), 5.25 (s, 2H), 4.44 (d, 1H, J = 6.8 Hz), 3.91 (dt, 1H, Ja = 6.6 and Jb = 3.1 Hz), 2.33 (s, 3H),

1.33 (dd, 2H, Ja = 8.6 and Jb = 3.7 Hz), 1.5 (d, 4H, J = 10.3 Hz), 1.39-1.29 (m, 2H), 1.18-1.13 (m, 1H),

1.07-1.00 (m, 2H). 13

C NMR (CDCl3, 100 MHz): δC = 162.2, 149.4, 148.1, 138.2, 134.6, 131.8, 130.1,

127.5, 126.6, 126.5, 126.4, 117.7, 117.8, 49.9, 44.6, 32.5, 25.5, 24.2, 21.1.


+: 382.1681; found: 398.1680.

6-Chloro-2-(Cyclohexylamino)-3-(3,4-dimethoxybenzyl)quinazolin-4(3H)-one (5p) : White solid

(72%), Mp 124-126 oC. [TLC control Rf(1) = 0.30, Rf(5p) = 0.60 (petroleum ether/ethyl acetate 8:2, UV

detection)].

IR (MIR-ATR, 4000–600 cm-1

): ʋmax = 3416, 3018, 2932, 2855, 1665, 1561, 1473, 1260, 1214, 1140,

1025, 746, 664.

1H NMR (CDCl3, 400 MHz): δH = 8.1 (d, 1H, J = 2.4 Hz), 7.47 (dd, 1H, Ja = 8.8 and Jb = 2.4 Hz), 7.29-

7.26 (m, 1H), 6.83-6.76 (m, 3H), 5.21 (s, 2H), 4.56 (d, 1H, J =6.8 Hz), 3.94-3.87 (m, 1H), 3.85 (s, 3H),

3.80 (s, 3H), 1.85 (d, 2H, J = 8.8 Hz), 1.53 (d, 3H, J = 8.3 Hz), 1.39-1.30 (m, 2H), 1.23-1.00 (m, 3H).

13C NMR (CDCl3, 100 MHz): δC = 162.3, 150.0, 149.5, 149.1, 148.1, 134.6, 127.5, 126.6, 126.5, 119.0,

117.7, 111.5, 109.7, 56.0, 55.9, 49.9, 44.7, 32.6, 25.5, 24.5.

HR-MS (ESI+) m/z calculated for [C23H27ClN3O3]+ = [M+H]

+: 428.1735; found: 428.1735.

6-Chloro-2-(Cyclohexylamino)-3-(4-fluorobenzyl)quinazolin-4(3H)-one (5q): White solid (68%), Mp

124-126 oC. [TLC control Rf(1) = 0.30, Rf(5q) = 0.70 (petroleum ether/ethyl acetate 8:2, UV detection)].

IR (MIR-ATR, 4000–600 cm-1

): ʋmax = 3435, 2930, 2854, 1659, 1557, 1310, 1129, 1066, 894, 750, 663.

1H NMR (CDCl3, 400 MHz): δH = 8.1 (d, 1H, J = 2.4 Hz), 7.50-7.48 (m, 1H), 7.30 (d, 1H, J = 8.8 Hz),

7.26-7.21 (m, 2H), 7.05 (t, 2H, J = 8.6 Hz), 5.25 (s, 2H), 4.32 (d, 1H, J = 6.8 Hz), 3.96-3.89 (m, 1H), 1.86

(dd, 3H, Ja = 12.0 and Jb = 3.2 Hz), 1.52 (dd, 3H, Ja = 9.0 and Jb = 4.4 Hz), 1.41-1.30 (m, 2H), 1.19-1.13

(m, 1H), 1.07-0.98 (m, 2H). 13

C NMR (CDCl3, 100 MHz): δC = 163.8, 162.1, 149.0, 148.0, 134.7, 130.8,

130.7, 128.4, 128.3, 127.6, 126.7, 126.4, 117.6, 116.5, 116.3, 50.0, 44.0, 32.6, 25.5, 24.3.

HR-MS (ESI+) m/z calculated for [C21H22ClFN3O]+ = [M+H]

+: 386.1430; found: 386.1431.

S8

6-chloro-3-(2-Chlorobenzyl)-2-(cyclohexylamino)quinazolin-4(3H)-one (5r): White solid (72%), Mp

120-122 oC. [TLC control Rf(1) = 0.30, Rf(5r) = 0.50 (petroleum ether/ethyl acetate 8:2, UV detection)].

IR (MIR-ATR, 4000–600 cm-1

): ʋmax = 3431, 2923, 2852, 1672, 1559, 1472, 1329, 1135, 1033, 824, 745,

622.

1H NMR (CDCl3, 400 MHz): δH = 8.12 (d, 1H, J = 2 Hz), 7.51 (dd, 1H, Ja = 8.8 and Jb = 2.4 Hz), 7.43 (d,

1H, J = 7.8 Hz), 7.31-7.26 (m, 2H), 7.24-7.19 (m, 2H), 7.13-7.11 (m, 1H), 5.42 (s, 2H), 4.42 (d, 1H, J =

6.8 Hz), 3.95 (dtd, 1H, Ja = 10.1, Jb = 6.1 and Jc = 3.9 Hz), 1.89-1.86 (m, 2H), 1.57 (d, 3H, J = 8.3 Hz),

1.40-1.30 (m, 2H), 1.19-1.04 (m, 3H). 13

C NMR (CDCl3, 100 MHz): δC = 162.3, 148.6, 134.8, 132.4,

132.3, 129.7, 129.5, 128.2, 128.0, 127.6, 126.7, 126.5, 117.5, 50.2, 41.2, 32.6, 25.5, 24.5.

HR-MS (ESI+) m/z calculated for [C21H22Cl2N3O]+ = [M+H]

+: 402.1134; found: 402.1134.

6-Chloro-3-(2-(1H-indol-2-yl)ethyl)-2-(cyclohexylamino)quinazolin-4(3H)-one (5s): Pale yellow

(62%), Mp 142-144 oC. [TLC control Rf(1) = 0.30, Rf(5m) = 0.50 (petroleum ether/ethyl acetate 8:2, UV

detection)].

IR (MIR-ATR, 4000–600 cm-1

): ʋmax = 3443, 3373, 2928, 2854, 1669, 1558, 1473, 1344, 1217, 1131,

1067, 896, 749, 662.

1H NMR (CDCl3, 400 MHz): δH = 8.28 (br s, 1H), 8.08 (d, 1H, J = 2.4 Hz), 7.65 (d, 1H, J = 7.8 Hz),

7.45-7.38 (m, 2H), 7.26-7.15 (m, 3H), 6.91 (d, 1H, J = 2Hz), 4.26 (t, 2H, J = 6.1 Hz), 3.74 (d, 1H, J = 7.3

Hz), 3.5 (dtt, 1H, Ja = 10.9, Jb = 7.1 and Jc = 3.6 Hz), 3.26 (t, 2H, J = 6.1 Hz), 1.52-1.41 (m, 5H), 1.26-

1.09 (m, 4H). 13

C NMR (CDCl3, 100 MHz): δC = 162.2, 149.3, 147.9, 136.7, 134.4, 127.3, 126.5, 126.0,

123.1, 122.9, 120.4, 118.0, 117.9, 112.0, 111.9,49.8, 43.6, 31.9, 25.5, 24.8, 24.1.


+: 421.1790; found: 421.1788.

S9

Copies of 1H,

13C NMR spectra of all compounds (5a-5s)

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0

Chemical Shift (ppm)

3.712.543.232.281.030.992.081.132.464.221.091.00

8.1

975

8.1

779

8.1

743

7.5

827

7.3

871

7.3

663

7.3

566

7.3

382

7.3

199

7.3

028

7.2

783

7.2

600

7.1

720

5.3

227

4.3

706

4.3

535

3.9

941

3.9

709

3.9

611

3.9

526

3.9

464

3.9

281

2.1

962

1.8

454

1.8

246

1.8

148

1.4

970

1.4

616

1.3

614

1.3

528

1.3

345

1.3

271

1.1

426

1.0

350

1.0

094

0.0

034

1H NMR (400MHz) spectrum of compound 5a in CDCl3

S10

160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0


163.

3943

149.

6940

149.

3951

135.

5562

134.

5865

129.

5993

128.

4837

127.

5723

126.

8432

125.

2026

122.

6434

117.

1312

77.6

343

77.3

208

77.0

000

49.9

566

44.8

090

32.7

274

25.8

006

24.4

299

13C NMR (100MHz) spectrum of compound 5a in CDCl3.

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0


2.181.132.333.182.143.181.031.032.082.061.082.001.041.061.00

8.1

98.1

98.1

7

7.5

87.5

67.5

67.3

87.3

67.2

27.2

07.1

97.1

77.1

56.8

96.8

7

5.2

6

4.4

54.4

33.9

93.9

83.9

73.9

63.9

53.9

53.9

33.7

9

1.8

81.8

61.8

61.5

41.5

31.5

21.3

81.3

81.3

61.3

5

1.0

61.0

4

1H NMR (400MHz) spectrum of compound 5b in CDCl3

S11

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0


163.4

1

159.7

5

149.6

8149.5

2

134.5

1128.2

1127.5

3127.4

3125.1

7122.5

8117.2

0114.9

6

77.6

477.3

277.0

0

55.5

7

49.9

9

44.3

5

32.8

1

25.8

324.5

0

13C NMR (100MHz) spectrum of compound 5b in CDCl3.

9 8 7 6 5 4 3 2 1 0


2.151.172.303.272.533.221.031.002.135.251.041.051.00

8.1

926

8.1

730

7.5

998

7.5

961

7.5

790

7.5

619

7.5

582

7.3

798

7.3

590

7.1

867

4.4

060

4.3

889

3.9

929

3.9

831

3.9

660

3.9

599

3.9

501

3.9

416

3.9

354

2.3

318

1.8

747

1.8

662

1.8

442

1.8

356

1.5

166

1.4

909

1.3

724

1.3

638

1.3

467

1.3

381

1.0

485

1.0

228

1H NMR (400MHz) spectrum of compound 5c in CDCl3.

S12

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0


163.4

454

149.7

013

149.5

409

138.2

978

134.5

573

132.4

647

130.2

555

127.5

942

126.8

650

125.1

953

122.6

215

117.2

041

77.6

343

77.3

135

77.0

000

50.0

077

44.6

996

32.8

003

25.8

663

24.5

028

21.3

967

13C NMR (100MHz) spectrum of compound 5c in CDCl3.

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0


2.782.833.003.562.862.832.901.080.952.003.001.011.041.000.97

8.1

767

8.1

596

7.5

912

7.5

741

7.5

558

7.5

521

7.3

724

7.3

517

7.2

600

7.1

818

7.1

622

7.1

439

6.8

285

6.7

882

5.2

408

4.5

172

4.4

989

3.9

636

3.9

562

3.9

477

3.9

391

3.9

318

3.8

597

3.8

377

3.8

132

2.1

864

1.8

808

1.8

600

1.8

539

1.5

435

1.5

227

1.3

797

1.3

711

1.3

528

1.3

455

1.2

452

1.0

888

1.0

582

1.0

326

0.8

676

-0.0

112

1H NMR (400MHz) spectrum of compound 5d in CDCl3.

S13

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0


163.4

745

150.1

753

149.6

503

149.3

003

134.5

865

128.0

754

127.5

796

125.1

953

122.6

215

119.2

457

117.1

676

111.6

919

109.9

566

77.6

343

77.3

208

77.0

000

56.2

417

56.2

199

49.9

931

44.8

528

32.8

440

25.8

371

24.5

028

13C NMR (100MHz) spectrum of compound 5d in CDCl3.

9 8 7 6 5 4 3 2 1 0


2.161.122.333.250.522.193.251.050.992.111.012.141.061.351.011.071.00

8.1

88.1

88.1

68.1

67.5

87.3

87.3

57.2

77.2

57.1

66.8

66.8

56.8

46.8

36.8

0

4.4

04.3

93.9

93.9

73.9

63.9

53.9

43.9

33.7

6

1.8

61.8

51.8

31.8

21.5

11.4

91.4

81.3

71.3

41.3

4

1.0

51.0

3

1H NMR (400MHz) spectrum of compound 5e in CDCl3.

S14

160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0


163

.10

160

.48

149

.42

149

.21

136

.95

134

.32

130

.42

127

.33

124

.92

122

.37

118

.76

116

.85

113

.76

112

.18

77.

3277.

2077.

0076.

68

55.

31

49.

70

44.

60

32.

47

25.

5524.

15

13C NMR (100MHz) spectrum of compound 5e in CDCl3.

9 8 7 6 5 4 3 2 1 0


2.151.152.363.162.161.020.992.082.101.082.291.041.051.00

8.1

88.1

88.1

68.1

67.5

97.3

97.3

7

7.2

67.2

67.2

47.1

87.0

87.0

67.0

4

5.2

9

4.2

74.2

64.0

03.9

93.9

83.9

73.9

63.9

5

1.9

01.8

91.8

71.8

61.5

41.5

11.3

91.3

81.3

61.3

61.0

51.0

2

1H NMR (400MHz) spectrum of compound 5f in CDCl3.

S15

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10


163

.70

163

.07

161

.24

149

.34

148

.90

134

.43

131

.06

128

.37

128

.29

127

.27

124

.97

122

.50

116

.80

116

.41

116

.19

77.

3277.

0076.

69

49.

78

43.

89

32.

60

25.

5224.

25

13C NMR (100MHz) spectrum of compound 5f in CDCl3.

9 8 7 6 5 4 3 2 1 0


3.212.293.152.241.030.982.042.831.462.041.051.01

8.0

88.0

6

7.4

97.3

37.3

17.2

97.2

77.1

67.1

47.0

97.0

77.0

5

5.3

4

4.2

94.2

7

3.9

03.9

03.8

93.8

83.8

73.8

6

1.8

21.8

11.7

91.7

81.4

81.4

61.2

81.2

71.2

51.2

40.9

80.9

50.9

3

1H NMR (400MHz) spectrum of compound 5g in CDCl3.

S16

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0


163

.42

149

.72

148

.74

134

.73

132

.81

132

.63

129

.85

129

.62

128

.40

128

.10

127

.57

125

.22

122

.66

116

.93

77.

6377.

3277.

00

50.

32

41.

35

32.

91

25.

8024.

76

13C NMR (100MHz) spectrum of compound 5g in CDCl3.

9 8 7 6 5 4 3 2 1 0


1.163.125.531.961.040.982.030.932.121.400.960.991.111.061.001.00

8.4

08.0

38.0

17.5

57.5

47.4

17.2

77.2

57.1

37.1

17.0

57.0

37.0

1

6.7

7

4.1

84.1

74.1

53.6

23.6

03.4

43.4

33.4

23.4

23.4

13.1

63.1

53.1

3

1.4

41.4

11.3

61.3

31.1

31.0

81.0

51.0

20.9

90.7

70.7

60.0

90.0

60.0

3

1H NMR (400MHz) spectrum of compound 5h in CDCl3.

S17

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0


162.8

6

149.2

4148.9

4

136.3

4133.7

8126.4

3126.1

7124.4

2122.8

2122.3

5121.8

8119.8

4117.6

3116.6

6111.5

5111.4

8

77.0

076.8

876.6

976.3

7

49.2

8

43.0

9

31.5

325.1

424.5

424.4

123.7

3

13C NMR (100MHz) spectrum of compound 5h in CDCl3.

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0


10.101.032.191.122.524.281.081.01

8.1

816

8.1

791

8.1

620

7.5

668

7.3

724

7.3

504

7.3

321

7.3

187

7.3

003

7.2

600

7.2

417

7.1

818

7.1

622

5.2

885

4.3

082

1.6

083

1.3

846

1.3

418

1.3

064

1.2

660

1.2

562

1.2

391

0.8

639

0.8

456

0.8

370

0.0

560

-0.0

173

1H NMR (400MHz) spectrum of compound 5i in CDCl3.

S18

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0


163.

28

149.

0414

8.43

135.

4513

4.18

129.

3112

8.24

127.

2412

6.69

125.

2512

2.42

116.

93

77.3

177

.00

76.6

8

52.5

7

44.8

6

28.8

0

13C NMR (100MHz) spectrum of compound 5i in CDCl3.

S19

8 7 6 5 4 3 2 1 0


3.491.565.821.930.930.051.061.411.041.00

8.0

850

8.0

814

8.0

642

8.0

618

7.5

252

7.5

081

7.5

045

7.3

199

7.2

991

7.2

600

7.1

256

7.1

060

7.0

877

5.1

382

4.5

906

2.0

862

1.9

444

1.9

114

1.8

759

1.8

466

1.8

050

1.7

708

1.5

471

1.5

178

1.4

848

1.2

550

1.1

890

1.1

230

0.8

786

0.8

297

0.0

878

0.0

719

0.0

462

-0.0

015

1H NMR (400MHz) spectrum of compound 5j in CDCl3.

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0


163

.18

148

.35

147

.96

133

.52

126

.75

124

.42

121

.78

77.

0076.

6976.

37

52.

28

30.

0228.

9426.

2425.

34

13C NMR (100MHz) spectrum of compound 5j in CDCl3.

S20

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0


3.203.264.822.360.920.961.153.011.211.120.941.01

8.1

400

8.1

376

8.1

205

7.8

320

7.8

125

7.5

485

7.5

448

7.4

458

7.4

250

7.4

226

7.3

920

7.2

600

7.1

647

4.0

711

4.0

613

4.0

565

4.0

467

4.0

369

4.0

308

4.0

210

3.7

228

3.7

044

2.2

365

2.0

104

1.8

992

1.5

960

1.5

728

1.4

213

1.4

115

1.3

944

1.3

870

1.2

831

1.2

538

1.1

218

1.0

888

1.0

582

0.8

786

-0.0

015

1H NMR (400MHz) spectrum of compound 5k in CDCl3.

160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0


162.3

225

150.1

242

148.1

337

135.0

167

134.7

834

134.6

157

131.7

065

131.1

888

129.7

888

127.5

942

125.2

974

123.8

829

122.7

236

117.6

343

77.6

343

77.5

177

77.3

135

77.0

000

50.1

244

33.1

794

33.1

211

29.9

858

29.1

036

26.6

975

25.8

444

24.9

257

24.8

236

13C NMR (100MHz) spectrum of compound 5k in CDCl3.

S21

9 8 7 6 5 4 3 2 1 0


3.392.311.192.562.241.040.851.161.480.291.040.271.01

8.0

227

8.0

190

8.0

019

7.9

995

7.6

279

7.6

071

7.5

900

7.4

030

7.2

600

7.2

368

7.1

622

7.1

427

7.1

243

4.9

047

3.8

462

3.8

206

3.8

108

3.8

010

3.7

766

2.0

788

2.0

715

2.0

483

2.0

409

1.7

708

1.7

464

1.7

366

1.4

445

1.4

139

1.2

721

1.2

489

1.2

428

1.2

122

1H NMR (400MHz) spectrum of compound 5l in CDCl3.

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10


160.3

685

150.9

335

136.9

416

129.4

389

129.0

305

125.0

203

124.4

881

123.7

006

120.1

789

113.4

491

77.6

343

77.3

208

77.0

000

50.4

889

33.2

305

25.7

350

24.9

184

13C NMR (100MHz) spectrum of compound 5l in CDCl3.

S22

9 8 7 6 5 4 3 2 1 0


1.062.273.963.342.501.000.982.146.361.080.88

8.1

315

8.1

254

7.5

118

7.4

898

7.3

651

7.3

468

7.3

321

7.3

126

7.2

906

7.2

600

7.2

441

5.2

995

4.3

962

4.3

779

3.9

354

3.9

293

3.9

208

3.9

122

3.9

061

1.8

270

1.8

050

1.7

965

1.4

983

1.4

628

1.3

516

1.3

430

1.3

259

1.3

174

1.2

514

1.0

252

0.9

996

0.8

492

-0.0

039

1H NMR (400MHz) spectrum of compound 5m in CDCl3.

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0


162

.4829

149

.5190

148

.3233

135

.2281

134

.9146

129

.7159

128

.6660

127

.8275

126

.8505

126

.7630

117

.9843

77.

6343

77.

3135

77.

0000

50.

1098

45.

0059

32.

7274

29.

9786

25.

7861

24.

4445

13C NMR (100MHz) spectrum of compound 5m in CDCl3.

S23

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0


2.733.393.492.563.211.000.962.052.142.071.301.151.00

8.1

193

8.1

131

7.4

983

7.4

922

7.4

763

7.4

702

7.3

016

7.2

796

7.2

600

7.1

964

7.1

757

6.8

884

6.8

664

5.2

225

4.4

806

4.4

635

3.9

306

3.9

232

3.9

147

3.9

061

3.8

988

3.7

814

3.7

521

1.8

613

1.8

393

1.8

307

1.5

386

1.5

227

1.5

117

1.3

663

1.3

394

1.3

320

1.2

514

1.0

509

1.0

252

0.8

737

-0.0

039

1H NMR (400MHz) spectrum of compound 5n in CDCl3.

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0


162

.1548

159

.5154

149

.3003

147

.9733

134

.4844

127

.9004

127

.3973

126

.7265

126

.5515

126

.3692

117

.7072

114

.7105

77.

3208

77.

0000

76.

6865

55.

2720

49.

7962

44.

2038

32.

4722

29.

6359

25.

4725

24.

1893

13C NMR (100MHz) spectrum of compound 5n in CDCl3.

S24

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0


2.401.242.653.522.363.431.121.082.324.571.471.151.00

8.1

303

8.1

241

7.5

081

7.5

020

7.4

861

7.4

800

7.3

077

7.2

869

7.2

600

7.1

549

7.1

512

5.2

518

4.4

451

4.4

280

3.9

306

3.9

232

3.9

147

3.9

061

3.8

988

2.3

331

1.8

490

1.8

393

1.8

270

1.8

185

1.5

166

1.4

909

1.3

638

1.3

553

1.3

369

1.3

284

1.0

424

1.0

167

1H NMR (400MHz) spectrum of compound 5o in CDCl3.

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0


162

.5048

149

.6430

148

.3233

138

.4873

134

.8563

132

.1148

130

.3430

127

.7692

126

.8505

126

.7630

118

.0499

77.

6343

77.

5177

77.

3208

77.

0000

50.

1389

44.

8528

32.

7711

25.

8225

24.

4955

21.

4186

13C NMR (100MHz) spectrum of compound 5o in CDCl3.

S25

9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0


3.602.192.912.002.672.870.850.931.922.931.230.990.86

8.1

046

8.0

985

7.4

886

7.4

825

7.4

666

7.4

605

7.2

930

7.2

710

7.2

600

6.8

347

6.8

151

6.7

907

6.7

613

5.2

066

4.5

637

4.5

466

3.9

220

3.9

159

3.9

061

3.8

988

3.8

914

3.8

743

3.8

499

3.8

034

1.8

613

1.8

393

1.5

361

1.5

154

1.3

626

1.3

553

1.3

357

1.3

296

1.2

330

1.1

536

1.0

509

1.0

252

0.8

297

-0.0

210

1H NMR (400MHz) spectrum of compound 5p in CDCl3.

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0


162

.4684

150

.1680

149

.6940

149

.3513

148

.2649

134

.7980

127

.6671

126

.8578

126

.6682

119

.2165

117

.9551

111

.6700

109

.8982

77.

6343

77.

5177

77.

3135

77.

0000

56.

2053

56.

1834

50.

0952

44.

9475

32.

7711

25.

7569

24.

4663

13C NMR (100MHz) spectrum of compound 5p in CDCl3.

S26

8 7 6 5 4 3 2 1 0


2.321.232.613.572.601.131.092.292.252.401.231.121.00

8.1

046

8.0

985

7.5

069

7.4

849

7.3

077

7.2

857

7.2

539

7.2

404

7.2

331

7.2

197

7.0

730

7.0

522

5.2

530

4.3

327

4.3

156

3.9

648

3.9

489

3.9

403

3.9

318

3.9

232

3.9

159

1.8

747

1.8

674

1.8

454

1.8

368

1.5

374

1.5

276

1.5

154

1.5

044

1.3

736

1.3

467

1.0

448

1.0

191

0.9

874

-0.0

076

1H NMR (400MHz) spectrum of compound 5q in CDCl3.

160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0


164

.0141

162

.3882

161

.5569

149

.2638

148

.2431

134

.9657

130

.9992

130

.9700

128

.6514

128

.5712

127

.8931

126

.9452

126

.6755

117

.9041

116

.7593

116

.5406

77.

6343

77.

5250

77.

3208

77.

0000

50.

2046

44.

2986

32.

8294

25.

7496

24.

5393

13C NMR (100MHz) spectrum of compound 5q in CDCl3.

S27

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0


3.602.673.552.391.141.072.301.101.562.161.131.151.00

8.1

205

8.1

156

7.5

216

7.4

996

7.4

935

7.4

421

7.4

226

7.3

187

7.2

967

7.2

600

7.2

099

7.1

378

5.4

181

4.4

256

4.4

085

3.9

807

3.9

636

3.9

550

3.9

464

3.9

379

3.9

293

3.9

220

1.8

955

1.8

833

1.8

723

1.8

649

1.5

838

1.5

630

1.3

699

1.3

626

1.3

430

1.3

345

1.1

010

1.0

754

1.0

485

-0.0

027

1H NMR (400MHz) spectrum of compound 5r in CDCl3.

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0


162

.5413

148

.8628

148

.3524

135

.0604

132

.6689

132

.5231

129

.9638

129

.8180

128

.4545

128

.2212

127

.8494

126

.9307

126

.7557

117

.7947

77.

6343

77.

3135

77.

0000

50.

5035

41.

4842

32.

9169

25.

7934

24.

8017

13C NMR (100MHz) spectrum of compound 5r in CDCl3.

S28

8 7 6 5 4 3 2 1 0


1.353.595.561.990.960.932.000.973.482.081.020.950.97

8.2

806

8.0

814

8.0

752

7.6

352

7.4

470

7.4

311

7.4

250

7.4

006

7.3

810

7.2

453

7.2

209

7.1

989

7.1

720

6.9

141

6.9

092

6.5

939

4.2

789

4.2

642

4.2

483

3.7

497

3.7

313

3.5

138

3.5

040

3.4

954

3.4

857

3.4

771

3.2

718

3.2

571

3.2

412

2.0

336

1.7

268

1.5

276

1.4

897

1.4

836

1.4

494

1.2

440

1.1

817

1.1

597

1.1

524

1.1

279

0.8

773

0.8

480

0.1

831

0.1

574

0.1

281

0.1

012

-0.0

112

1H NMR (400MHz) spectrum of compound 5s in CDCl3

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0


161

.8559

149

.3513

147

.5650

136

.3218

134

.0324

126

.9598

126

.1505

125

.6328

122

.7236

122

.5122

119

.9894

117

.6270

117

.5176

111

.6190

111

.4732

77.

0000

76.

6792

76.

3657

49.

3806

43.

2341

31.

4951

25.

1153

24.

5611

24.

4153

23.

6716

13C NMR (100MHz) spectrum of compound 5s in CDCl3

S29

References:

1. Ji. F, Lv. M-F, Yi. W-B and Cai. C., One-pot synthesis of 2-amino-4(3H)-quinazolinones via ring-opening of isatoic anhydride and

palladium-catalyzed oxidative isocyanide-insertion. Org. Biomol. Chem., 2014, 12, 5766

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