Sodium hydride → 1-(3-{[tert-Butyl(dimethyl)silyl]oxy}propyl)-8-(4-fluorophenyl)-N,N,2-trimethyl-1,6,7,8-tetrahydrochromeno[7,8-d]imidazole-5-carboxamide

HRID 1258471ノート

反応式

HRID 1258471 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][C:11]3[C:14]([C:22]([N:24]([CH3:26])[CH3:25])=[O:23])=[CH:15][C:16]4[NH:17][C:18]([CH3:21])=[N:19][C:20]=4[C:10]=3[O:9]2)=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:30][CH2:31][CH2:32][O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35]>CN(C)C=O>[Si:34]([O:33][CH2:32][CH2:31][CH2:30][N:19]1[C:20]2[C:10]3[O:9][CH:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)[CH2:13][CH2:12][C:11]=3[C:14]([C:22]([N:24]([CH3:25])[CH3:26])=[O:23])=[CH:15][C:16]=2[N:17]=[C:18]1[CH3:21])([C:37]([CH3:38])([CH3:39])[CH3:40])([CH3:36])[CH3:35]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 607486(3-Bromopropoxy)(tert-butyl)dimethylsilaneHCID 672205608-(4-Fluorophenyl)-N,N,2-trimethyl-3,6,7,8-tetrahydrochromeno[7,8-d]imidazole-5-carboxamide

生成物 1

HCID 672206591-(3-{[tert-Butyl(dimethyl)silyl]oxy}propyl)-8-(4-fluorophenyl)-N,N,2-trimethyl-1,6,7,8-tetrahydrochromeno[7,8-d]imidazole-5-carboxamide収率 46%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

To a solution of 8-(4-fluorophenyl)-N,N,2-trimethyl-3,6,7,8-tetrahydrochromeno[7,8-d]imidazole-5-carboxamide (52.0 mg, 0.147 mmol, Step 8) in N,N-dimethylformamide (1.5 mL), was added sodium hydride (7.1 mg, 0.18 mmol) at 0° C. and the mixture was stirred at 0° C. for 30 minutes. Then (3-bromopropoxy)(tert-butyl)dimethylsilane (48.4 mg, 0.191 mmol) was added to the mixture at 0° C. The mixture was allowed to warm to room temperature, stirred for 4 hours and left at the same temperature overnight. The reaction was quenched by saturated ammonium chloride aqueous solution. The mixture was extracted with ethyl acetate. The combined organic layers were washed with water and brine. It was dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC eluting with hexane/ethyl acetate (1:1 and then 1:4) to afford the title compound as a brown oil (35.5 mg, 46%).

後処理

  1. temperatureto warm to room temperature
  2. stirringstirred for 4 hours
  3. waitleft at the same temperature overnight
  4. customThe reaction was quenched by saturated ammonium chloride aqueous solution
  5. extractionThe mixture was extracted with ethyl acetate
  6. washThe combined organic layers were washed with water and brine
  7. dry with materialIt was dried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by preparative TLC
  10. washeluting with hexane/ethyl acetate (1:1

出典と根拠

ORDレコード
ord-ac9b887ae13b479eb8587769359f923e
出典データセット
uspto-grants-2013_06
特許番号
US08466166B2

反応ノート

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