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, , 1988.
, tert-butylamino)-1-(4-chlorophenyl
, , pp.416-187
, This compound was synthesized according to the general procedure II-A, using 4chlorobenzaldehyde (141 mg, 1.0 mmol), propylamine (0.08 ml, 1.0 mmol), 4methoxybenzoic acid (152 mg, 1.0 mmol) and tert-butyl isocyanide
, Purification by flash chromatography using (Et 2 O : DCM = 5 : 95) gave the desired product in 77 % isolated yield (320 mg, 0.77 mmol). Nature: Light yellow oil
H-b,c,f), 6.84 (d, J = 8.8 Hz, 2H, H-g), 6.35 (br s, 1H, NH), 5.47 (s, 1H, H-1), 3.76 (s, 3H, H-6), CDCl 3 , 400 MHz): ? (ppm) 7.38-7.24 (m, 6H ,
,
, C-f), vol.130
, HRMS: Calculated for, pp.316-1106
, , vol.3425, pp.1033-1034, 1095.
, tert-butyl)-2-oxo-3-(pyridin-2-yl)azetidin-3-yl)-N-propylacetamide C 17 H, vol.25
, , pp.303-195
, This compound was synthesized according to the general procedure III-A, using Ugi adduct II-53 (146 mg, 0.5 mmol), sodium hydride (50 mg, 1.25 mmol) and diiodomethane (0.06 ml, 0.75 mmol). Purification by flash chromatography using
, CDCl 3 , 400 MHz): ? (ppm) 8.49 (d, J = 4.2 Hz, 1H, H-e), 7.54 (td, J = 7.7, 1.4 Hz, vol.1
, , vol.3
,
CDCl 3 , 100.6 MHz): ? (ppm) 171.3 (C-6), 164.2 (C-2), vol.156 ,
C-d), 74.2 (C-1), vol.122 ,
, HRMS: Calculated for C 17 H 25 N 3 O 2 : 303, p.303, 1941.
, , vol.3058, 1247.
tert-butyl)-2-(4-chlorophenyl)-3-iodo-2-(N-propylacetamido)propanamide ,
, , pp.338-176
, This compound was separated during the reaction of Ugi adduct II-40 (162 mg, vol.0
, sodium hydride (50 mg, 1.25 mmol) and diiodomethane (0.06 ml, 0.75 mmol) in DMF according to the general procedure III-Aduring one of the optimization trials. Purification by flash chromatography using, vol.10, p.90
09 (d, J = 8.6 Hz, 2H, H-b), 6.96 (br s, 1H, NH), CDCl 3 , 400 MHz): ? (ppm) 7.19 (d, J = 8.8 Hz, 2H, H-c), vol.7 ,
,
, C-1), 51.0 (C-3), vol.126
, HRMS: Calculated for, pp.239-1044
, , vol.3431, pp.1099-57, 1225.
, , pp.371-173
, This compound was synthesized according to the general procedure III-B, using 2(3,4-dimethoxyphenyl)ethylamine (0.34 ml, 2.0 mmol) and diethyl 2-phenylmalonate, p.56
, Purification by flash chromatography using
, Nature: Yellow oil
76 (br s, 1H, NH), 6.69 (d, J = 8.0 Hz, 1H, H-i), CDCl 3 , 400 MHz): ? (ppm) 7.23 (br s, vol.6, pp.61-67 ,
C-5), 149.0 (C-h), CDCl 3 , 100.6 MHz): ? (ppm) 170.8 (C-3), vol.167 ,
, C-4), 58.6 (C-2), vol.61
, , vol.3430, pp.1028-1029, 1190.
, Ethyl 3-(cyclohexylamino)-3-oxo-2-phenylpropanoate C 17 H 23 NO 3
, , pp.289-168
, This compound was synthesized according to the general procedure III-B, using cyclohexylamine (0.23 ml, 2.0 mmol) and diethyl 2-phenylmalonate (0.56 ml, 2.6 mmol)
, Purification by flash chromatography using gradient eluent (DCM : Et 2 O =, vol.100, pp.0-98
, CDCl 3 , 400 MHz): ? (ppm) 7.34-7.24 (m, 5H, H-Ar), vol.6
,
C-5), CDCl 3 , 100.6 MHz): ? (ppm) 171.1 (C-3), vol.166 ,
,
, , vol.3420, pp.1030-1031, 1163.
, chlorophenyl)amino)-3-oxo-2-phenylpropanoate C 17 H 16 ClNO 3, Ethyl, vol.3, issue.4
, , pp.317-082
, This compound was synthesized according to the general procedure III-B, using 4chloroaniline (255 mg, 2.0 mmol) and diethyl 2-phenylmalonate (0.56 ml, 2.6 mmol)
, Purification by flash chromatography using gradient eluent
, CDCl 3 , 400 MHz): ? (ppm) 9.12 (br s, 1H, NH), 7.39 (d, J = 8.8 Hz, 2H, H-f), vol.7
CDCl 3 , 100.6 MHz): ? (ppm) 171.3 (C-3), vol.165 ,
, , vol.3334, pp.1029-1030, 1094.
, Ethyl 3-oxo-2-phenyl-3-((1-phenylethyl)amino)propanoate C 19 H 21 NO 3
, , pp.311-152
, This compound was synthesized according to the general procedure III-B, using (R)1-phenylethyl amine (0.26 ml, 2.0 mmol) and diethyl 2-phenylmalonate
, Purification by flash chromatography using, vol.50, p.50
, CDCl 3 , 400 MHz): ? (ppm) (mixture of diastereomers 1:1) 7.48-7.28 (m, 10H, HAr),5.17 (2q, J = 7.0 Hz, vol.1
CDCl 3 , 100.6 MHz): ? (ppm) (mixture of diastereomers 1:1) 171.0 (C-3), vol.166 ,
, C-a), 129.1 (C-c), 129.0 (Cc), vol.166
, , vol.3423, pp.1030-1031, 1164.
, , pp.277-168
, This compound was synthesized according to the general procedure III-B, using tertbutyl amine (0.21 ml, 2.0 mmol) and diethyl 2-benzylmalonate (0.61 ml, 2.6 mmol)
, Purification by flash chromatography using, vol.2, p.98
, CDCl 3 , 400 MHz): ? (ppm) 7.32-7.21 (m, 5H, H-Ar), vol.6
, CDCl 3 , 100.6 MHz): ? (ppm), vol.171
, , vol.3438, pp.1221-1032, 1254.
, III-62
, Ethyl 2-(tert-butylcarbamoyl)pent-4-enoate C 12 H 21 NO 3
, , pp.227-152
, This compound was synthesized according to the general procedure III-B, using tertbutyl amine (0.21 ml, 2.0 mmol) and diethyl 2-allylmalonate (0.52 ml, 2.6 mmol)
, Purification by flash chromatography using gradient eluent
, CDCl 3 , 400 MHz): ? (ppm) 6.38 (br s, 1H, NH), 5.78 (ddt, J = 17.1, 10.1, 7.0 Hz, vol.1
, CDCl 3 , 100.6 MHz): ? (ppm) 171.8 (C-3), 166.8 (C-5), vol.134
, , vol.3436, 1367.
tert-butyl)-2-cyano-2-phenylacetamide C 13 H 16 N 2 O ,
, , pp.216-126
, This compound was synthesized according to the general procedure III-B, using tertbutyl amine (0.21 ml, 2.0 mmol) and ethyl 2-cyano-2-phenylacetate
, Purification by flash chromatography using gradient eluent
, CDCl 3 , 400 MHz): ? (ppm) 7.47 (br s, vol.5
, CDCl 3 , 100.6 MHz): ? (ppm) 162.6 (C-3), vol.131
, HRMS: Calculated for, pp.173-1232
, , vol.3421, pp.1456-64, 1496.
tert-butyl)-2-methyl-3-oxobutanamide C 9, vol.17 ,
, , pp.171-126
, This compound was synthesized according to the general procedure III-B, using tertbutyl amine (0.21 ml, 2.0 mmol) and ethyl 2-acetyl-2-methylacetate
, Purification by flash chromatography using gradient eluent
400 MHz): ? (ppm) 5.80 (br s, 1H, NH), 3.20 (q, J = 7.1 Hz, vol.1, issue.3 ,
, CDCl 3 , 100.6 MHz): ? (ppm), vol.207
, HRMS: Calculated for C 9 H 17 NO 2 : 171.1259, p.171, 1255.
, , vol.3436, 1169.
, III-65
, , pp.191-131
, A solution of tert-butyl amine (0.21 ml, 2.0 mmol) and triethylamine (0.28 ml
, mmol) in dichloromethane (2 ml) at 0 °C was treated with 2-phenylacetyl chloride (0, vol.27
, The residue was purified by flash chromatography using
,
, CDCl 3 , 400 MHz): ? (ppm) 7.42-7.38 (m, 2H, H-Ar), vol.5, p.27
MHz): ? (ppm) 170.3 (C-2), vol.135, pp.28-35 ,
, , vol.3419, pp.1220-1031, 1366.
, , pp.275-152
, using ethyl 3-(tert-butylamino)-3-oxo-2-phenylpropanoate III-54 (132 mg, 0.5 mmol), sodium hydride (50 mg, 1.25 mmol) and diiodomethane (0.06 ml, 0.75 mmol). Purification by flash chromatography using
, CDCl 3 , 400 MHz): ? (ppm) 7.52 (d, J = 7.3 Hz, 2H, H-b)
,
CDCl 3 , 100.6 MHz): ? (ppm) 169.1 (C-3), vol.162 ,
, HRMS: Calculated for, pp.176-0829
, , vol.3090, 1227.
, , pp.259-121
, using ethyl 3-(allylamino)-3-oxo-2-phenylpropanoate III-56(124 mg, 0.5 mmol), sodium hydride (50 mg, 1.25 mmol) and diiodomethane (0.06 ml, 0.75 mmol). Purification by flash chromatography using (Et 2 O : PE = 40 : 60) gave the desired product in 65 % isolated yield (84 mg, 0.32 mmol), Nature: Light yellow oil
, CDCl 3 , 400 MHz): ? (ppm) 7.41 (d, J = 7.5 Hz, 2H, H-b)
,
42 (d, AX system, J ax = 5.5 Hz, 2H, H-6), 3.83 (dd, ABX system, J ab = 15.7, J ax = J bx = 5.9 Hz, vol.2 ,
, CDCl 3 , 100.6 MHz): ? (ppm) 168.7 (C-3), 164.1 (C-5), vol.135, pp.131-132
, , vol.3089, 1221.
, , pp.383-173
, 4-dimethoxyphenethyl)amino)-3-oxo-2-phenylpropanoate III-57 (186 mg, 0.5 mmol), sodium hydride (50 mg, 1.25 mmol) and diiodomethane (0.06 ml, 0.75 mmol). Purification by flash chromatography using (Et 2 O : PE = 70 : 30) gave the desired, vol.3
, Nature: Yellow oil
,
, CDCl 3 , 400 MHz): ? (ppm) 7.31-7.21, vol.58, pp.6-67
,
C-b), 128.1 (C-d), 127.1 (C-c), 120.6 (C-j), 111.6 (C-f), CDCl 3 , 100.6 MHz): ? (ppm) 168.7 (C-3), vol.164, pp.51-53 ,
, , vol.3064, 1261.
, , pp.301-168
, This compound was synthesized according to the general procedure III-C, usingethyl 3-(cyclohexylamino)-3-oxo-2-phenylpropanoate III-58 (145 mg, 0.5 mmol), sodium hydride (50 mg, 1.25 mmol) and diiodomethane (0.06 ml, 0.75 mmol). Purification by flash chromatography using
, CDCl 3 , 400 MHz): ? (ppm) 7.41-7.38 (m, 2H, H-b), vol.2
CDCl 3 , 100.6 MHz): ? (ppm) 169.0 (C-3), 163.4 (C-5), vol.135 ,
, C-6), 30.6 (C-Cy), 30.5 (CCy), vol.127
, , pp.1099-1027, 1220.
, , pp.329-082
, chlorophenyl)amino)-3-oxo-2-phenylpropanoate III-59 (159 mg, 0.5 mmol), sodium hydride (50 mg, 1.25 mmol) and diiodomethane (0.06 ml, 0.75 mmol). Purification by flash chromatography using, vol.3
, CDCl 3 , 400 MHz): ? (ppm) 7.49-7.45 (m, 2H, H-b), vol.2
CDCl 3 , 100.6 MHz): ? (ppm)168.1 (C-3), vol.160 ,
, , vol.3067, 1095.
, IV-11
, N-(4-methylbenzyl)-2-(N-propylacetamido)acetamide C 21 H 25 ClN 2 O 2
, , pp.372-161
, This compound was synthesized according to the general procedure II-A, using 4chlorobenzaldehyde (141 mg, 1.0 mmol), propylamine (0.08 ml, 1.0 mmol)
, mmol) and 1-(isocyanomethyl)-4-methylbenzene (131 mg, 1.0 mmol). Purification by flash chromatography using gradient eluent, vol.80, pp.20-100
16 (br s, 4H, H-f,g), 6.71 (br s, 1H, NH), 5.92 (s, 1H, H-1), 4.45 (dd, ABX system, J ab = 14.0, J ax = 6.0, J bx = 5.6 Hz, 2H, H-3), 3.30 (ddd, J = 9, CDCl 3 , 400 MHz): ? (ppm) 7.36 (br s, vol.4 ,
, CDCl 3 , 100.6 MHz): ? (ppm) 171.7 (C-5), 169.5 (C-2), 137.1 (C-h), vol.134
, HRMS: Calculated for C 21 H 25 ClN 2 O 2 : 372.1605, pp.372-1596
, , vol.3433, p.15, 1140.
, , pp.320-341
, This compound was synthesized according to the general procedure II-A, using 3methoxybenzaldehyde (0.12 ml, 1.0 mmol), propylamine (0.08 ml, 1.0 mmol), acetic acid (0.06 ml, 1.0 mmol) and tert-butyl isocyanide (0.11 ml, 1.0 mmol). Purification by flash chromatography using, vol.20, p.80
H-b), 6.86 (br s, 1H, H-f), 6.80 (dd, J = 8.2, 2.2 Hz, 1H, H-d), CDCl 3 , 400 MHz): ? (ppm) 7.20 (t, J = 7.9 Hz, 1H, H-c), 6.90 (d, J = 7.7 Hz, vol.1 ,
,
, C-d), 62.4 (C-1), 121.6 (C-b), 114.8 (C-f), vol.113
, HRMS: Calculated for, pp.221-1417
, , vol.3425, p.8, 1223.
, tert-butyl)-3-(4-chlorophenyl)-5-methylene-2-oxopyrrolidin-3-yl
, , pp.362-176
, This compound was synthesized according to the general procedure IV-A, using N(tert-butyl)-2-(4-chlorophenyl)-2-(N-propylacetamido)acetamide II-40(130 mg, 0.4 mmol), sodium hydride (40 mg, 1.0 mmol)
, 4 mmol). Purification by flash chromatography using, vol.70, p.30
, CDCl 3 , 400 MHz): ? (ppm) 7.46 (d, J = 8.7 Hz, 2H, H-b), 7.26 (d, J = 8.8 Hz, vol.2
, CDCl 3 , 100.6 MHz): ? (ppm) 173.1 (C-2), vol.171, pp.142-148
, , pp.1096-1107, 1214.
, chlorophenyl)-1-cyclohexyl-5-methylene-2-oxopyrrolidin-3-yl
, , pp.388-192
, This compound was synthesized according to the general procedure IV-A, using 2-(4chlorophenyl)-N-cyclohexyl-2-(N-propylacetamido)acetamide II-46 (140 mg, 0.4 mmol), sodium hydride (40 mg, 1.0 mmol)
, Purification by flash chromatography using (Et 2 O : PE = 70 : 30) gave the desired product in 78 % isolated yield
, Nature, pp.129-131
,
, CDCl 3 , 400 MHz): ? (ppm) 7.42 (d, J = 8.7 Hz, 2H, H-b), 7.24 (d, J = 8.8 Hz, vol.2
, CDCl 3 , 100.6 MHz): ? (ppm) 172.8 (C-2), 171.7 (C-4), 142.4 (C-10), vol.135
, 28.3 (C-Cy), 27.5 (C-Cy), 26.1 (C-Cy), 26.0 (C-Cy), 25.4 (C-Cy), vol.23
, HRMS: Calculated for C 22 H 29 ClN 2 O 2 : 388, p.388, 1918.
, , vol.1015, 1103.
, chlorophenyl)-1-(4-methylbenzyl)-5-methylene-2-oxopyrrolidin-3-yl
, , pp.410-176
, This compound was synthesized according to the general procedure IV-A, using 2-(4chlorophenyl)-N-(4-methylbenzyl
, propargyl bromide (0.07 ml, 0.6 mmol) and TBAF (0.4 ml, 0.4 mmol). Purification by flash chromatography using, sodium hydride (40 mg, 1.0 mmol)
, Nature, pp.96-98
, CDCl 3 , 400 MHz): ? (ppm) 7.61 (d, J = 8.6 Hz, 2H, H-c), 7.41 (d, J = 8.6 Hz, 2H, H-b), 7.06 (d, J = 7.8 Hz, 2H, H-f), 6.96 (d, J = 7.9 Hz, vol.2
,
CDCl 3 , 100.6 MHz): ? (ppm) 173.1 (C-2), vol.171 ,
, 134.5 (C-d), vol.132
, HRMS: Calculated for C 24 H 27 ClN 2 O 2 : 410.1761, pp.410-1749
, , pp.1096-1110, 1251.
, tert-butyl)-5-methylene-2-oxo-3-(3-(trifluoromethyl)phenyl)pyrrolidin-3-yl
, , pp.396-203
, (trifluoromethyl)phenyl)acetamide III-31(143 mg, 0.4 mmol), sodium hydride (40 mg, 1.0 mmol), propargyl bromide (0.07 ml, 0.6 mmol) and TBAF (0.4 ml, 0.4 mmol). Purification by flash chromatography using, This compound was synthesized according to the general procedure IV-A, using N(tert-butyl
, Nature, pp.95-97
, CDCl 3 , 400 MHz): ? (ppm) 7.72-7.70 (m, 2H, H-d,f), 7.51 (d, J = 7.7 Hz, 1H, Hb), vol.7
, CDCl 3 , 100.6 MHz): ? (ppm) 172.7 (C-2), 171.6 (C-5), 142.4 (C-11), vol.138
, HRMS: Calculated for C 21 H 27 F 3 N 2 O 2 : 396, p.396, 2018.
, , vol.1079, 1133.
, tert-butyl)-3-(3-methoxyphenyl)-5-methylene-2-oxopyrrolidin-3-yl
, , pp.358-226
, This compound was synthesized according to the general procedure IV-A, using N(tert-butyl)-2-(3-methoxyphenyl
, sodium hydride (40 mg, 1.0 mmol), propargyl bromide (0.07 ml, 0.6 mmol) and TBAF (0.4 ml, 0.4 mmol). Purification by flash chromatography using
, CDCl 3 , 400 MHz): ? (ppm) 7.31 (t, J = 8.2 Hz, vol.1
,
, 113.5 (C-f), vol.119
, HRMS: Calculated for C 21 H 30 N 2 O 3 : 358.2256, p.358, 2243.
, , pp.1150-1037, 1215.
, tert-butyl)-5-methylene-2-oxo-3-(pyridin-2-yl)pyrrolidin-3-yl)-N-propylacetamide C 19 H, vol.27
, , pp.329-350
, This compound was synthesized according to the general procedure IV-A, using N(tert-butyl)-2-(N-propylacetamido)-2-(pyridin-2-yl)acetamide II-53 (117 mg, 0.4 mmol), sodium hydride (40 mg, 1.0 mmol)
, 4 mmol). Purification by flash chromatography using, vol.70, p.30
, CDCl 3 , 400 MHz): ? (ppm) 8.61 (d, J = 4.8 Hz, 1H, H-e), 7.77 (d, J = 7.9 Hz, 1H, H-b), 7.71 (td, J = 7.7, 1.8 Hz, vol.1
CDCl 3 , 100.6 MHz): ? (ppm) 173.3 (C-2), vol.171 ,
, C-d), 90.1 (C-12), 69.8 (C-1), vol.123
, , vol.3059, pp.1260-1153, 1410.
, tert-butyl)-5-methylene-2-oxo-3-(thiophen-2-yl)
, , pp.334-172
, This compound was synthesized according to the general procedure IV-A, using N(tert-butyl)-2-(N-propylacetamido)-2-(thiophen-2-yl)acetamide III-33 (119 mg, 0.4 mmol), sodium hydride (40 mg, 1.0 mmol)
, Purification by flash chromatography using (Et 2 O : PE = 70 : 30) gave the desired product in 70 % isolated yield (94 mg, 0.28 mmol). Nature: Deep yellow solid
, , pp.132-134
400 MHz): ? (ppm) 7.40 (dd ,
H-12), 4.30 (br s, 1H, H-12), 3.45 (dt, J = 14.1, 2.3 Hz, vol.1 ,
, CDCl 3 , 100.6 MHz): ? (ppm) 173.2 (C-2), vol.170, p.41
, , vol.1148, 1214.
, IV-19
, , pp.426-171
, This compound was synthesized according to the general procedure IV-A, using N(tert-butyl)-2-(4-chlorophenyl)-2-(N-(4-methoxyphenyl)acetamido)acetamide II-55 (156 mg, 0.4 mmol), sodium hydride (40 mg, 1.0 mmol), propargyl bromide (0.07 ml, 0.6 mmol) and TBAF (0.4 ml, 0.4 mmol). Purification by flash chromatography using, vol.60, p.40
14 (d, J = 8.8 Hz, 2H, H-b), 6.99 (br s, 2H, H-f), 6.70 (br s, 2H, CDCl 3 , 400 MHz): ? (ppm) 7.38 (d, J = 8.8 Hz, 2H, H-c), vol.7 ,
,
, 90.6 (C-10), 69.4 (C-1), vol.129
, , vol.3008, pp.1096-1116, 1250.
, , pp.426-171
, This compound was synthesized according to the general procedure IV-A, using N(tert-butyl)-2-(4-chlorophenyl)-2-(N-(4-methoxybenzyl)acetamido)acetamide II-56 (161 mg, 0.4 mmol), sodium hydride (40 mg, 1.0 mmol), propargyl bromide (0.07 ml, 0.6 mmol) and TBAF (0.4 ml, 0.4 mmol). Purification by flash chromatography using
H-b), 6.85 (s, 4H, H-f,g), 4.67 (d, CDCl 3 , 400 MHz): ? (ppm) 7.42 (d, J = 8.7 Hz, 2H, H-c), 7.28 (d, J = 8.7 Hz, vol.2 ,
CDCl 3 , 100.6 MHz): ? (ppm) 173.1 (C-2), vol.171, pp.142-148 ,
, 129.1 (C-e), vol.128, pp.90-91
, , pp.1096-1117, 1176.
, , pp.454-202
, tert-butylamino)-1-(4-chlorophenyl)-2-oxoethyl)-4-methoxy-N-propylbenzamide III-42 (167 mg, 0.4 mmol), sodium hydride (40 mg, 1.0 mmol), propargyl bromide (0.07 ml, 0.6 mmol) and TBAF (0.4 ml, 0.4 mmol). Purification by flash chromatography using
, Nature, pp.147-149
H-b), 6.95 (d, J = 8.8 Hz, CDCl 3 , 400 MHz): ? (ppm) 7.70 (d, J = 8.7 Hz, vol.2 ,
,
, 129.6 (C-b), 129.0 (C-e), vol.128
, , pp.1095-1014, 1251.
, , pp.390-207
, This compound was synthesized according to the general procedure IV-A, using N(tert-butyl)-2-(4-chlorophenyl)-2-(N-propylacetamido)acetamide II-40 (130 mg, 0.4 mmol), sodium hydride (40 mg, 1.0 mmol
, 4 mmol). Purification by flash chromatography using, vol.50, p.50
, CDCl 3 , 400 MHz): ? (ppm) 7.48 (s, 1H, NH), 7.30 (s, 4H, H-b,c), 3.48 (ddd, J = 15.7, 10.7, 4.9 Hz, vol.1, pp.3-39
, , vol.3
400 MHz): ? (ppm), vol.172 ,
, HRMS: Calculated for C 17 H 21 ClNO, pp.290-1306
, , vol.3379, pp.1097-1015, 1223.
, chlorophenyl)-1-(3,4-dimethoxyphenethyl)-5-methylene-2-oxopyrrolidin-3-yl
, , pp.470-197
, This compound was synthesized according to the general procedure IV-A, using 2-(4chlorophenyl)-N-(3,4-dimethoxyphenethyl)-2-(N-propylacetamido)acetamide III-29 (173 mg, 0.4 mmol), sodium hydride (40 mg, 1.0 mmol)
H-f), 6.61 (d, J = 8.1 Hz, 1H, H-i), 6.54 (dd, J = 8.1, 1.4 Hz, 1H, H-j), 4.18 (d, J = 8.7 Hz, 2H, H-12), 3.76 (s, 3H, OMe), 3.75 (s, 3H, OMe), 3.63-3.46 (m, 2H, H-3), 3.38 (d, AB system, CDCl 3 , 400 MHz): ? (ppm) 7.41, vol.1 ,
Ch), 142.3 (C-11), CDCl 3 , 100.6 MHz): ? (ppm) ? 172.6 (C-2), vol.171 ,
, HRMS: Calculated for C 26 H 31 ClN 2 O 4 : 470, p.470, 1971.
, , pp.1157-1198, 1262.
, 4-chlorophenyl)-8,9-dimethoxy-10b-methyl-3-oxo-1,2,3,5, vol.6, p.10
, , pp.470-197
, This compound was synthesized according to the general procedure IV-B, using 2-(4chlorophenyl)-N-(3,4-dimethoxyphenethyl)-2-(N-propylacetamido)acetamide III-29 (173 mg, 0.4 mmol), sodium hydride (40 mg, 1.0 mmol)
, 4 mmol) and trifluoracetic acid (0.06 ml, 0.8 mmol). Purification by flash chromatography using gradient eluent
, , pp.107-109
,
50 (s, 1H, H-f), 6.46 (s, 1H, H-i), 4.24 (dd, J = 13.0, 5.1 Hz, 1H, H-3), 3.80 (s, 3H, OMe), 3.77 (s, 3H, OMe), 3.19 (d, AB system, CDCl 3 , 400 MHz): ? (ppm) 7.78 (d, J = 8.7 Hz, 2H, H-c), 7.33 (d, J = 8.7 Hz, 2H, H-b), vol.6 ,
,
, CDCl 3 , 100.6 MHz): ? (ppm) 171.3 (C-5), vol.170, pp.27-32
, HRMS: Calculated for C 26 H 31 ClN 2 O 4 : 470, p.470, 1958.
, , vol.3064, pp.957-958, 1097.
, , pp.399-216
, This compound was synthesized according to the general procedure II-A, using pyridine-2-carboxaldehyde (0.1 ml, 1.0 mmol), propylamine (0.08 ml, 1.0 mmol), acetic acid (0.06 ml, 1.0 mmol) and4-(2-isocyanoethyl)-1,2-dimethoxybenzene
, Purification by flash chromatography using (MeOH : DCM = 4 : 96) gave the desired product in 94 % isolated yield (377 mg, 0.94 mmol). Nature: Deep yellow oil
,
, CDCl 3 , 400 MHz): ? (ppm) 8.48 (d, J = 4.1 Hz, 1H, H-e), vol.7
56 (s, 1H, H-1), 3.88 (s, 3H, OMe), 3.83 (s, 3H, OMe), vol.5 ,
C-a), 148.8 (C-h), CDCl 3 , 100.6 MHz): ? (ppm) 171.5 (C-5), 168.5 (C-2), vol.156 ,
, , vol.3437, pp.1030-1031, 1194.
, 4-dimethoxyphenethyl)-2-(naphthalen-2-yl
, , pp.448-236
, This compound was synthesized according to the general procedure II-A, using naphthalene-2-carboxaldehyde (156 mg, 1.0 mmol), propylamine (0.08 ml, 1.0 mmol), acetic acid (0.06 ml, 1.0 mmol) and4-(2-isocyanoethyl)-1,2-dimethoxybenzene
, Purification by flash chromatography using (pure EtOAc) gave the desired product in 94 % isolated yield (420 mg, 0.94 mmol)
, CDCl 3 , 400 MHz): ? (ppm) 7.89-7.81 (m, 4H, H-c
,
94 (s, 1H, H-1), 3.81 (s, 3H, OMe), 3.74 (s, 3H, OMe), 3.64 (td, J =, vol.5, issue.7 ,
H-3), 3.38-3.24 (m, 2H, 3.48 (td, J = 13.0, 6.7 Hz, vol.1 ,
,
C-i), CDCl 3 , 100.6 MHz): ? (ppm)171.6 (C-5), vol.169 ,
, 126.8 (C-b), 126.6 (C-f), vol.126
, HRMS: Calculated, pp.448-2367
, , vol.3297, p.47, 1026.
, , pp.496-177
, This compound was synthesized according to the general procedure II-A, using 4chlorobenzaldehyde (141 mg, 1.0 mmol), 4-methoxyaniline (123 mg, 1.0 mmol), acetic acid (0.06 ml, 1.0 mmol) and 4-(2-isocyanoethyl)-1,2-dimethoxybenzene
, Purification by flash chromatography using (EtOAc : PE = 80 : 20) gave the desired product in 83 % isolated yield (413 mg, 0.83 mmol)
, Nature, pp.71-73
,
H-b), 6.76-6.69 (m, 4H, H-Ar), 6.65 (dd, J = 8.1, 1.4 Hz, 1H, H-j), CDCl 3 , 400 MHz): ? (ppm) 7.15 (d, J = 8.4 Hz, 2H, H-c), 7.02 (d, J = 8.4 Hz, vol.2 ,
,
C-i), 147.6 (C-h), 134.4 (C-k), 131.8 (C-d), 131.2 (C-b), 131.2 (C-l), 128.5 (C-c), 120.7 (C-f), 114.1 (C-m), vol.148 ,
, HRMS: Calculated for C 27 H 29 ClN 2 O 5 : 496.1765, p.496, 2088.
, , vol.3314, pp.906-724, 1028.
, , pp.474-229
, This compound was synthesized according to the general procedure II-A, using 4chlorobenzaldehyde (141 mg, 1.0 mmol), propylamine (0.08 ml, 1.0 mmol), pivalic acid (102 mg, 1.0 mmol) and4-(2-isocyanoethyl)-1,2-dimethoxybenzene
, Purification by flash chromatography using (pure Et 2 O) gave the desired product in 68 % isolated yield (325 mg, 0.68 mmol). Nature: Light yellow oil
H-i), 6.63 (d, J = 1.9 Hz, 1H, H-f), 6.56 (dd, J = 8.1, 1.9 Hz, 1H, H-j), CDCl 3 , 400 MHz): ? (ppm) 7.19 (d, J = 8.6 Hz, vol.2 ,
C-b), 128.8 (C-c), 120.6 (C-j), 111.8 (C-f), 111.2 (C-i), 67.3 (C-1), CDCl 3 , 100.6 MHz): ? (ppm) 178.3 (C-5), 170.1 (C-2), 149.0 (C-h), vol.147 ,
, , vol.3436, p.44, 1194.
, , pp.437-232
, This compound was synthesized according to the general procedure IV-B, using N(3,4-dimethoxyphenethyl)-2-(N-propylacetamido)-2-(pyridin-2-yl)acetamide IV-43 (160 mg, 0.4 mmol), sodium hydride (40 mg, 1.0 mmol)
, 4 mmol) and trifluoracetic acid (0.06 ml, 0.8 mmol). Purification by flash chromatography using gradient eluent, EtOH : EtOAc =, vol.2, pp.98-106
, Nature: Yellow oil. R f
25-7.21 (m, 1H, H-d), 6.54 (s, 1H, H-j), 6.49 (s, 1H, vol.1 ,
C-i), 147.4 (C-h), CDCl 3 , 100.6 MHz): ? (ppm) 171.2 (C-5), vol.170, pp.43-51 ,
, , vol.3057, pp.927-722, 1023.
, 9-dimethoxy-10b-methyl-2-(naphthalen-2-yl)-3-oxo-1,2,3,5,6,10bhexahydropyrrolo
, , pp.486-252
, This compound was synthesized according to the general procedure IV-B, using N(3,4-dimethoxyphenethyl)-2-(naphthalen-2-yl)-2-(N-propylacetamido)acetamide IV-45 (179 mg, 0.4 mmol), sodium hydride (40 mg, 1.0 mmol)
, 4 mmol) and trifluoracetic acid (0.06 ml, 0.8 mmol). Purification by flash chromatography using gradient eluent, EtOH : EtOAc =, vol.2, pp.98-102
, , pp.257-259
,
(m, 2H, H-g,f), 6.63 (d, J = 2.5 Hz, 2H, H-o,l), 4.40 (dd, CDCl 3 , 400 MHz): ? (ppm) 8.36 (s, 1H, H-j), 8.07 (d, J = 8.7 Hz, 1H, H-b), 7.987.95 (m, 2H, H-h,e), 7.94-7.89 (m, 1H, vol.12 ,
, CDCl 3 , 100.6 MHz): ? (ppm) 171.4 (C-5), 170.5 (C-2), vol.147
, HRMS: Calculated for C 30 H, pp.486-2499
, , vol.3057, pp.757-758, 1022.
, IV-48
, 4-chlorophenyl)-8,9-dimethoxy-10b-methyl-3-oxo-1,2,3,5,6,10bhexahydropyrrolo[2,1-a]isoquinolin-2-yl)-N-(4-methoxyphenyl)acetamide C 30 H 31 ClN 2 O 5
, , pp.534-192
, This compound was synthesized according to the general procedure IV-B, using 2-(4chlorophenyl
, IV-47 (199 mg, 0.4 mmol), sodium hydride (40 mg, 1.0 mmol), p.0
H-l), 6.62 (dd, J = 8.4, 2.5 Hz, 1H, H-i), 6.53 (s, 1H, Hf), CDCl 3 , 400 MHz): ? (ppm) 7.37 (d, J = 8.3 Hz, 2H, H-c), 7.02 (d, J = 8.9 Hz, 2H, H-b), 6.81 (dd, J = 13.1, 8.7 Hz, vol.2 ,
, CDCl 3 , 100.6 MHz): ? (ppm) 171.9 (C-5), 170.0 (C-2), vol.158
, C-i), 107.8 (C-f), 71.4 (C-1), vol.124
, HRMS: Calculated for C 30 H 31 ClN 2 O 5 : 534, p.534, 1921.
, , vol.910, pp.734-735, 1037.
, 4-chlorophenyl)-8,9-dimethoxy-10b-methyl-3-oxo-1,2,3,5, vol.6, p.10
, , pp.512-244
, 4-dimethoxyphenethyl)amino)-2-oxoethyl)-N-propylpivalamide IV-49 (190 mg, 0.4 mmol), sodium hydride (40 mg, 1.0 mmol)
, TBAF (0.4 ml, 0.4 mmol) and trifluoracetic acid (0.06 ml, 0.8 mmol). Purification by flash chromatography using gradient eluent, vol.5, p.90
52 (s, 1H, H-i), 6.50 (s, 1H, H-f), 4.18 (dd, J = 13.0, 5.0 Hz, 1H, H-3), 3.83 (s, 3H, OMe), 3.79 (s, 3H, OMe), 3.59-3.48 (m, 1H, H-8), 3.38 (d, AB system, CDCl 3 , 400 MHz): ? (ppm)7.74 (d, J = 8.5 Hz, 2H, H-b), 7.29 (d, J = 8.9 Hz, vol.2 ,
C-a), 135.3 (C-j), 134.1 (C-d), 129.5 (C-b), CDCl 3 , 100.6 MHz): ? (ppm) 178.8 (C-5), vol.170, pp.29-35 ,
, HRMS: Calculated for, p.371, 1298.
, , vol.850, pp.749-750, 1013.
, , pp.369-113
, 9dimethoxy-10b-methyl-3-oxo-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinolin-2-yl)-Npropylacetamide IV-41 (141 mg, 0.3 mmol) with 1 equiv. of tosic acid (57 mg, 0.3 mmol) in reduced pressure. Purification by flash chromatography using, vol.8
H-b), 6.70 (s, 1H, H-i), CDCl 3 , 400 MHz): ? (ppm) 7.78 (d, J = 8.7 Hz, 2H, H-c), 7.40 (s, 1H, H-5), 7.27 (d, J = 8.7 Hz, vol.2 ,
C-j), 112.1 (C-f), 109.1 (C-i), 62.8 (C-6, CDCl 3 , 100.6 MHz): ? (ppm) 168.7 (C-2), vol.148 ,
, , vol.3073, pp.1093-1016, 1130.
, , pp.446-197
, This compound was synthesized according to the general procedure II-A, using 4chlorobenzaldehyde (141 mg, 1.0 mmol), vol.3
, acetic acid (0.057 ml, 1.0 mmol) and tert-butyl isocyanide (0.11 ml, 1.0 mmol)
, Purification by flash chromatography using, vol.20, p.80
H-b,c), 6.76 (d, J = 8.1 Hz, 1H, H-i), 6.52 (dd, CDCl 3 , 400 MHz): ? (ppm) 7.45 (d, J = 8.4 Hz, vol.4 ,
C-h), 134.6 (C-)a, 134.4 (C-d), 131.1 (C-c), CDCl 3 , 100.6 MHz): ? (ppm) 171.6 (C-5), 168.8 (C-2), vol.148, pp.49-50 ,
, HRMS: Calculated for, p.346, 1211.
, , vol.3426, pp.1179-1094, 1247.
, IV-54
, , pp.350-221
, 4dimethoxybenzaldehyde (166 mg, 1.0 mmol), propylamine (0.082 ml, 1.0 mmol), acetic acid (0.057 ml, 1.0 mmol) and tert-butyl isocyanide (0.11 ml, 1.0 mmol). Purification by flash chromatography using (EtOAc : P.E. = 70 : 30) gave the desired, vol.3
, Nature: Yellow solid
,
400 MHz): ? (ppm) 6.88 (d, J = 10.5 Hz, 2H, H-b,f), 6.77 (d, J = 8.1 Hz, vol.1, issue.3 ,
09 (s, 3H, H-6), 1.37-1.24 (m, vol.2 ,
, CDCl 3 , 100.6 MHz): ? (ppm) 171.4 (C-5), 169.4 (C-2), vol.148
, HRMS: Calculated for C 19 H 30 N 2 O 4 : 350.2206, pp.350-2212
, , vol.3425, pp.1144-1027, 1264.
, Titre : Réactions multicomposants pour la préparation de composés hétérocycliques azotés à haut potentiel biologique Mots clés : Réactions Multicomposants, Réaction Ugi, Réaction Tsuji-Trost