Diisopropylethylamine → 2-{[(4-Tert-butoxycarbonyl-4-tert-butoxycarbonylamino-butyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-methyl}-benzoimidazole-1-carboxylic acid tert-butyl ester

HRID 1624260Notes

Reaction equation

HRID 1624260 reaction equation
[C:1]([O:5][C:6](=[O:30])[C@@H:7]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:8][CH2:9][CH2:10][NH:11][CH:12]1[C:21]2[N:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH2:15][CH2:14][CH2:13]1)([CH3:4])([CH3:3])[CH3:2].[C:31]([O:35][C:36]([N:38]1[C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=2[N:40]=[C:39]1[CH2:47]Cl)=[O:37])([CH3:34])([CH3:33])[CH3:32].C(N(CC)C(C)C)(C)C>CC#N>[C:31]([O:35][C:36]([N:38]1[C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=2[N:40]=[C:39]1[CH2:47][N:11]([CH2:10][CH2:9][CH2:8][CH:7]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:30])[NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:12]1[C:21]2[N:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH2:15][CH2:14][CH2:13]1)=[O:37])([CH3:34])([CH3:33])[CH3:32]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 15829159tert-Butyl 2-(chloromethyl)-1H-benzimidazole-1-carboxylateHCID 69157433(2S)-2-(tert-butoxycarbonylamino)-5-(5,6,7,8-tetrahydroquinolin-8-ylamino)-pentanoic acid tert-butyl ester

Product 1

HCID 692967622-{[(4-Tert-butoxycarbonyl-4-tert-butoxycarbonylamino-butyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-methyl}-benzoimidazole-1-carboxylic acid tert-butyl esterYield 77%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Using the General Procedure for N-alkylation: A solution of (2S)-2-(tert-butoxycarbonylamino)-5-(5,6,7,8-tetrahydroquinolin-8-ylamino)-pentanoic acid tert-butyl ester (0.700 g, 1.67 mmol), 1-(tert-butoxycarbonyl)-2-(chloromethyl)-benzimidazole (0.690 g, 2.59 mmol) and N,N-diisopropylethylamine (0.60 mL, 3.44 mmol) in CH3CN (16 mL) was heated at 60° C. for 24 hours. Purification of the crude material by column chromatography on silica gel (50:1 CH2Cl2—MeOH) provided 0.830 g (77%) of 2-{[(4-tert-butoxycarbonyl-4-tert-butoxycarbonylamino-butyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-methyl}-benzoimidazole-1-carboxylic acid tert-butyl ester as a tan foam.

Workup

  1. customPurification of the crude material by column chromatography on silica gel (50:1 CH2Cl2—MeOH)

Sources & evidence

ORD record
ord-321394f7110a49c0b923322833fb7462
Source dataset
uspto-grants-2014_07
Patent number
US08778967B2

Reaction notes

Loading…