Sodium hydride → 4-(1-cyclopropylmethyl-1H-benzoimidazol-2-yl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester

HRID 2230708노트

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HRID 2230708 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[NH:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:27][CH:28]1[CH2:30][CH2:29]1>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:16]([CH2:27][CH:28]3[CH2:30][CH2:29]3)[C:17]3[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=3[N:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 184646551-t-butoxycarbonyl-4-(1H-benzimidazol-2-yl)[1,4]diazepane

생성물 1

HCID 701476134-(1-cyclopropylmethyl-1H-benzoimidazol-2-yl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester수율 121.3%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

Treat a solution of 1-(t-butoxycarbonyl)-4-(1H-benzimidazol-2-yl)[1,4]diazepan (0.50 g, 1.58 mmol, Preparation 9) and dimethylformamide (10 mL) with sodium hydride (0.083 g, 2.08 mmol, 60% dispersion in oil) at room temperature. After 15 minutes, add (bromomethyl)cyclopropane (0.21 mL, 2.17 mmol, Aldrich Chemical Company) and heat two hours at 80° C. Cool the reaction and partition between dichloromethane (150 mL) and NaHCO3 solution (40 mL). Wash the organic phase with brine (40 mL), dry (MgSO4), filter and concentrate the filtrate to afford 4-(1-cyclopropylmethyl-1H-benzoimidazol-2-yl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester (0.71 g, Rf=0.87, silica gel, 95:5:0.5 dichloromethane:methanol:ammonium hydroxide).

후처리

  1. temperatureCool
  2. customthe reaction
  3. custompartition between dichloromethane (150 mL) and NaHCO3 solution (40 mL)
  4. washWash the organic phase with brine (40 mL)
  5. dry with materialdry (MgSO4)
  6. filtrationfilter
  7. concentrationconcentrate the filtrate

출처 및 근거

ORD 기록
ord-2f9590001cea458e984284c9bef64bc9
출처 데이터셋
uspto-grants-2002_07
특허 번호
US06423704B1

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