2-Chlorobenzimidazole → 1-ethoxycarbonyl-4-(1H-benzimidazol-2-yl)[1,4]diazepane
Reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:12][CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1)=[O:5])[CH3:2].Cl[C:14]1[NH:15][C:16]2[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=2[N:18]=1>CO>[CH2:1]([O:3][C:4]([N:6]1[CH2:12][CH2:11][CH2:10][N:9]([C:14]2[NH:18][C:17]3[CH:19]=[CH:20][CH:21]=[CH:22][C:16]=3[N:15]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 130 °C
Procedure
Combine 1-ethoxycarbonyl[1,4]diazepane (36.6 g, 212 mmol) and 2-chlorobenzimidazole (18.0 g, 106 mmol). Heat to 130° C. After 4 hours, cool to ambient temperature and add hot methanol to dissolve the reaction mixture. Partition the methanol solution between dichloromethane (700 mL) and a solution of sodium hydroxide (20 g) in water (500 mL). Separate the layers and extract the aqueous layer three times with dichloromethane. Combine the organic layers, extract with brine, dry over Na2SO4, filter, and evaporate in vacuo to give a solid. Triturate the solid with ethyl acetate (100 mL) and cool to 0° C. Collect solid by filtration and dry in vacuo to give 1-ethoxycarbonyl-4-(1H-benzimidazol-2-yl)[1,4]diazepane.
Workup
- temperaturecool to ambient temperature
- dissolutionto dissolve the reaction mixture
- customPartition the methanol solution between dichloromethane (700 mL)
- customSeparate the layers
- extractionextract the aqueous layer three times with dichloromethane
- extractionextract with brine
- dry with materialdry over Na2SO4
- filtrationfilter
- customevaporate in vacuo
- customto give a solid
- customTriturate the solid with ethyl acetate (100 mL)
- temperaturecool to 0° C
- customCollect solid
- filtrationby filtration
- customdry in vacuo
Sources & evidence
- ORD record
- ord-726d8a6cd92e46b3ab29b1549a13acec
- Source dataset
- uspto-grants-2002_07
- Patent number
- US06423704B1
Reaction notes
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