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

HRID 2230708Notes

Reaction equation

[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]

Participants

Conditions

Temperature: 80 °C

Procedure

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).

Workup

temperatureCool
customthe reaction
custompartition between dichloromethane (150 mL) and NaHCO3 solution (40 mL)
washWash the organic phase with brine (40 mL)
dry with materialdry (MgSO4)
filtrationfilter
concentrationconcentrate the filtrate

Sources & evidence

ORD record: ord-2f9590001cea458e984284c9bef64bc9
Source dataset: uspto-grants-2002_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06423704B1

Reaction notes

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