Dimethylformamide → 6-[(3-{[Tert-butyl(dimethyl)silyl]oxy}propyl)(methyl)amino]-2-chloro-5-fluoronicotinonitrile
反応式
[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]参加物
実験手順
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).
後処理
- 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
出典と根拠
- ORDレコード
- ord-741a933c33ab49dfafc8fe9010adde38
- 出典データセット
- uspto-grants-2010_05
- 特許番号
- US07714004B2
反応ノート
読み込み中…