Phosphorus oxychloride → 4-chloro-1-(5-fluoro-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidine
반응식
P(Cl)(Cl)([Cl:3])=O.[F:6][C:7]1[CH:8]=[CH:9][C:10]([CH3:23])=[C:11]([N:13]2[C:17]3[N:18]=[CH:19][NH:20][C:21](=O)[C:16]=3[CH:15]=[N:14]2)[CH:12]=1>>[Cl:3][C:21]1[N:20]=[CH:19][N:18]=[C:17]2[N:13]([C:11]3[CH:12]=[C:7]([F:6])[CH:8]=[CH:9][C:10]=3[CH3:23])[N:14]=[CH:15][C:16]=12참가 물질
반응 조건
- 온도
- 100 °C
실험 절차
Phosphorus oxychloride (5442 μl, 58.39 mmol) was added to 1-(5-fluoro-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (Intermediate AK2) (713 mg, 2.92 mmol), at ambient temperature. The resulting mixture was heated to 100° C. and stirred for 4 hours. The mixture was allowed to cool to ambient temperature. The reaction mixture was evaporated to near dryness. Dissolved into toluene, evaporated, dissolved, in toluene and evaporated to dryness again. The solid was dried under vacuum to give crude product. This was partitioned between EtOAc (70 mL), and water (25 mL). The organic phase was dried (MgSO4), evaporated, then dried under vacuum to afford the product (732 mg, 95%). 1H NMR (400 MHz, DMSO) δ 2.13 (3H, s), 7.52-7.42 (2H, m), 7.64-7.58 (1H, m), 8.83 (1H, s), 8.96 (1H, s); m/z (ES+) (M+H)+=263; HPLC tR=2.39 min.
후처리
- temperatureto cool to ambient temperature
- customThe reaction mixture was evaporated
- dissolutionDissolved into toluene
- customevaporated
- dissolutiondissolved, in toluene
- customevaporated to dryness again
- customThe solid was dried under vacuum
- customto give crude product
- customThis was partitioned between EtOAc (70 mL), and water (25 mL)
- dry with materialThe organic phase was dried (MgSO4)
- customevaporated
- customdried under vacuum
출처 및 근거
- ORD 기록
- ord-e232ddf316624d948fde3a9b245d208e
- 출처 데이터셋
- uspto-grants-2012_03
- 특허 번호
- US08143263B2
반응 노트
불러오는 중…