Dimethylformamide → 6-[(3-{[Tert-butyl(dimethyl)silyl]oxy}propyl)(methyl)amino]-2-chloro-5-fluoronicotinonitrile
반응식
[H-].[Na+].[Si:3]([O:10][CH2:11][CH2:12][CH2:13][NH:14][C:15]1[C:22]([F:23])=[CH:21][C:18]([C:19]#[N:20])=[C:17]([Cl:24])[N:16]=1)([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].[CH3:25]N(C=O)C>>[Si:3]([O:10][CH2:11][CH2:12][CH2:13][N:14]([CH3:25])[C:15]1[C:22]([F:23])=[CH:21][C:18]([C:19]#[N:20])=[C:17]([Cl:24])[N:16]=1)([C:6]([CH3:8])([CH3:9])[CH3:7])([CH3:5])[CH3:4]참가 물질
실험 절차
Sodium hydride (0.11 g, 4.65 mmol) was added to a solution of 6-[(3-{[tert-butyl(dimethyl)-14-silyl]oxy}propyl)amino]-2-chloro-5-fluoronicotinonitrile (Example 309, 0.80 9, 2.33 mmol) in DMF (23.26 mL). The mixture was stirred at rt for 30 min, and then Mel (0.58 mL, 9.30 mmol) added. The reaction mixture was stirred at rt for 18 h, quenched with water, and the aqueous phase was extracted with ether. The combined ether extracts were washed with water, brine, and then dried (MgSO4), filtered, and concentrated under reduced pressure. The product (0.88 g, 99%) was isolated after silica gel flash chromatography (2:1 hexanes/EtOAc). 1H NMR (400 MHz, CD3OD) δ 7.53 (d, 1H), 3.70-3.60 (m, 4H), 3.17 (d, 3H), 1.84-1.76 (m, 2H), 0.84 (s, 9H), 0.00 (s, 6H).
후처리
- additionMel (0.58 mL, 9.30 mmol) added
- stirringThe reaction mixture was stirred at rt for 18 h
- customquenched with water
- extractionthe aqueous phase was extracted with ether
- washThe combined ether extracts were washed with water, brine
- dry with materialdried (MgSO4)
- filtrationfiltered
- concentrationconcentrated under reduced pressure
출처 및 근거
- ORD 기록
- ord-741a933c33ab49dfafc8fe9010adde38
- 출처 데이터셋
- uspto-grants-2010_05
- 특허 번호
- US07714004B2
반응 노트
불러오는 중…