Dimethylformamide → 1-(3,4,5-Trimethoxybenzoyl)-3-(2-(4-(1-(4-cyanobutyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine

HRID 2230626Notes

Reaction equation

HRID 2230626 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:37]=[C:38]([O:42][CH3:43])[C:39]=1[O:40][CH3:41])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:19][CH2:20][N:21]2[CH2:27][CH2:26][CH2:25][N:24]([C:28]3[NH:32][C:31]4[CH:33]=[CH:34][CH:35]=[CH:36][C:30]=4[N:29]=3)[CH2:23][CH2:22]2)([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:9]1)=[O:7].CN(C)C=O.[H-].[Na+].Br[CH2:52][CH2:53][CH2:54][CH2:55][C:56]#[N:57]>CO.ClCCl.ClCCl.O>[CH3:43][O:42][C:38]1[CH:37]=[C:5]([CH:4]=[C:3]([O:2][CH3:1])[C:39]=1[O:40][CH3:41])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:19][CH2:20][N:21]2[CH2:27][CH2:26][CH2:25][N:24]([C:28]3[N:29]([CH2:52][CH2:53][CH2:54][CH2:55][C:56]#[N:57])[C:30]4[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=4[N:32]=3)[CH2:23][CH2:22]2)([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:9]1)=[O:7]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 794355-BromopentanenitrileHCID 184644781-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine

Product 1

HCID 184649071-(3,4,5-Trimethoxybenzoyl)-3-(2-(4-(1-(4-cyanobutyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

Combine 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine (0.1 g, 0.17 mmol) and dimethylformamide (2 mL). Add sodium hydride (8 mg, 60% in oil, 0.34 mmol). After 12 hours, add 1-bromo-4-cyanobutane (27 mg, 0.17 mmol). After 1.5 hours, add water (5 mL) and dichloromethane (20 mL). Separate the layers and extract the aqueous layer twice with dichloromethane. Combine the organic layers, dry over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 5% methanol/dichloromethane/0.5% concentrated aqueous ammonia to give the title compound: Rf=0.26 (silica gel, 5% methanol/dichloromethane/0.5% concentrated aqueous ammonia).

Workup

  1. waitAfter 1.5 hours
  2. customSeparate the layers
  3. extractionextract the aqueous layer twice with dichloromethane
  4. dry with materialdry over Na2SO4
  5. filtrationfilter
  6. customevaporate in vacuo
  7. customto give a residue

Sources & evidence

ORD record
ord-c2257168ff014a6185ab3c0e1556b4c5
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

Loading…