Potassium Cyanide → 5-((2R,4S)-4-cyano-2-(3-fluorophenyl)pyrrolidin-1-yl)-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide
反応式
CS(O[C@@H:6]1[CH2:10][C@H:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)[N:8]([C:18]2[CH:23]=[CH:22][N:21]3[N:24]=[CH:25][C:26]([C:27](=[O:47])[N:28]([CH2:38][C:39]4[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=4)[CH2:29][C:30]4[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=4)=[C:20]3[CH:19]=2)[CH2:7]1)(=O)=O.[C-:48]#[N:49].[K+]>CS(C)=O>[C:48]([C@@H:6]1[CH2:7][N:8]([C:18]2[CH:23]=[CH:22][N:21]3[N:24]=[CH:25][C:26]([C:27]([N:28]([CH2:29][C:30]4[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=4)[CH2:38][C:39]4[CH:40]=[CH:41][C:42]([O:45][CH3:46])=[CH:43][CH:44]=4)=[O:47])=[C:20]3[CH:19]=2)[C@@H:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)[CH2:10]1)#[N:49]参加物
4
反応条件
- 温度
- 90 °C
実験手順
A mixture of (3R,5R)-1-(3-(bis(4-methoxybenzyl)carbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-5-(3-fluorophenyl)pyrrolidin-3-yl methanesulfonate (I-34) (0.17 g, 0.26 mmol), potassium cyanide (20 mg, 0.31 mmol) and DMSO (anhyd, 1 mL) was heated at 90° C. for 3 hours. After cooling, the reaction mixture was partitioned in EtOAc and water. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by silica chromatography eluting with an EtOAc/Hex gradient to yield 5-((2R,4S)-4-cyano-2-(3-fluorophenyl)pyrrolidin-1-yl)-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide (I-35). 1H NMR (400 MHz, CDCl3) δ 8.15-8.11 (m, 1 H), 7.80 (s, 1 H), 7.37-7.28 (m, 1 H), 7.22-7.15 (m, 5 H), 7.02-6.93 (m, 2 H), 6.93-6.86 (m, 5 H), 6.15 (dd, J=2.7, 7.7 Hz, 1H), 5.08 (dd, J=2.6, 7.9 Hz, 1 H), 4.72 (d, J=15.7 Hz, 2 H), 4.54 (d, J=15.8 Hz, 2 H), 4.20-4.14 (m, 1 H), 3.91-3.83 (m, 1 H), 3.82 (s, 6 H), 3.37-3.24 (m, 1 H), 2.82 (ddd, J=8.1, 10.1, 12.4 Hz, 1 H), 2.41 (ddd, J=2.8, 6.4, 12.4 Hz, 1 H). MS m/z 590.2 (M+1)+