Trifluoroacetic acid → (2S,4R)-4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-N-methyl-pyrrolidine-2-carboxamide
반응식
C(O)(C(F)(F)F)=O.[NH2:8][C:9]1[N:14]=[CH:13][C:12]([C:15]2[CH:16]=[N:17][N:18]([C@H:20]3[CH2:24][N:23](C(OC(C)(C)C)=O)[C@H:22]([C:32](=[O:35])[NH:33][CH3:34])[CH2:21]3)[CH:19]=2)=[CH:11][C:10]=1[C:36]1[O:37][C:38]2[CH:44]=[CH:43][CH:42]=[CH:41][C:39]=2[N:40]=1>>[NH2:8][C:9]1[N:14]=[CH:13][C:12]([C:15]2[CH:16]=[N:17][N:18]([C@H:20]3[CH2:24][NH:23][C@H:22]([C:32]([NH:33][CH3:34])=[O:35])[CH2:21]3)[CH:19]=2)=[CH:11][C:10]=1[C:36]1[O:37][C:38]2[CH:44]=[CH:43][CH:42]=[CH:41][C:39]=2[N:40]=1참가 물질
반응 조건
- 온도
- 25 °C
실험 절차
TFA (5 ml) was added to (2S,4R)-tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-2-(methylcarbamoyl)pyrrolidine-1-carboxylate under argon. The resulting solution was stirred at 25° C. for 1 hour. The solution was evaporated under reduced pressure, adsorbed with ammonia in methanol solution. The crude product was purified by flash chromatography on silica gel eluting with 1 to 6% methanolic ammonia (7 N) in dichloromethane. The solvent was evaporated to dryness to afford (2S,4R)-4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-N-methyl-pyrrolidine-2-carboxamide (38 mg) as a pale yellow solid. 37% Aqueous formaldehyde (8.42 μl) at 0° C. was added to a stirred solution 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-N-methyl-pyrrolidine-2-carboxamide (38 mg) dissolved in methanol (2 ml) and dichloromethane (2 ml) over a period of 5 minutes under argon. The resulting solution was stirred at 0° C. for 5 minutes. Sodium triacetoxyhydroborate (23.96 mg, 0.11 mmol) was added and the mixture was stirred 5 minutes at 25° C. A solution of ammonia in methanol 7N (1 ml) was added and the mixture was adsorbed on silica gel. The crude product was purified by flash chromatography on silica gel eluting with 1 to 6% methanolic ammonia (7 N) in dichloromethane. The solvent was evaporated to dryness to afford (2S,4R)-4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-N,1-dimethyl-pyrrolidine-2-carboxamide (30 mg) after overnight stirring in acetonitrile as a solid. NMR Spectrum: (DMSOd6) 2.23-2.32 (m, 1H), 2.35 (s, 3H), 2.47-2.56 (m partially hidden by DMSOd5, 1H), 2.65 (d, 3H), 2.76-2.84 (m, 1H), 3.19-3.27 (m, 1H), 3.47-3.56 (m, 1H), 4.89-4.99 (m, 1H), 7.41-7.50 (m, 2H), 7.67 (bs, 2H), 7.77-7.82 (m, 1H), 7.83-7.87 (m, 1H), 7.90 (q, 1H), 7.97 (s, 1H), 8.37 (s, 1H), 8.44 (d, 1H), 8.53 (d, 1H) Mass spectrum: M+H+ 418
후처리
- customThe solution was evaporated under reduced pressure
- customThe crude product was purified by flash chromatography on silica gel eluting with 1 to 6% methanolic ammonia (7 N) in dichloromethane
- customThe solvent was evaporated to dryness
출처 및 근거
- ORD 기록
- ord-1d2a8787b7bd4c77b796ec23eab39ac1
- 출처 데이터셋
- uspto-grants-2011_09
- 특허 번호
- US08017611B2
반응 노트
불러오는 중…