Diisopropylethylamine → 2-{[[4-(tert-Butoxycarbonylamino-methyl)-benzyl]-(5,6,7,8-tetrahydro-quinolin-7-yl)-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl ester

HRID 2308291Notes

Reaction equation

HRID 2308291 reaction equation
[C:1]([O:5][C:6](=[O:27])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH:16][CH:17]2[CH2:26][C:25]3[N:24]=[CH:23][CH:22]=[CH:21][C:20]=3[CH2:19][CH2:18]2)=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[C:28]([O:32][C:33]([N:35]1[C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=2[N:37]=[C:36]1[CH2:44]Cl)=[O:34])([CH3:31])([CH3:30])[CH3:29].CCN(C(C)C)C(C)C>CC#N>[C:28]([O:32][C:33]([N:35]1[C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=2[N:37]=[C:36]1[CH2:44][N:16]([CH2:15][C:12]1[CH:13]=[CH:14][C:9]([CH2:8][NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:27])=[CH:10][CH:11]=1)[CH:17]1[CH2:26][C:25]2[N:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH2:19][CH2:18]1)=[O:34])([CH3:31])([CH3:30])[CH3:29]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 15829159tert-Butyl 2-(chloromethyl)-1H-benzimidazole-1-carboxylateHCID 68900505{4-[(5,6,7,8-Tetrahydro-quinolin-7-ylamino)-methyl]-benzyl}-carbamic acid tert-butyl ester

Product 1

HCID 689014482-{[[4-(tert-Butoxycarbonylamino-methyl)-benzyl]-(5,6,7,8-tetrahydro-quinolin-7-yl)-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl esterYield 56%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

{4-[(5,6,7,8-Tetrahydro-quinolin-7-ylamino)-methyl]-benzyl}-carbamic acid tert-butyl ester (88 mg, 0.24 mmol), 2-Chloromethyl-benzimidazole-1-carboxylic acid tert-butyl ester (80 mg, 0.30 mmol), DIPEA (0.10 mL, 0.54 mmol), and KI (19 mg, 0.11 mmol) were heated to 80° C. in CH3CN (1.5 mL) for 2 h under N2, then it was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo, diluted with ethyl acetate, washed with NH4Cl (aq), NaCl (aq), and dried (MgSO4). Evaporation of the solvent and purification of the residue by flash chromatography on silica gel (1:1:98 CH3OH—NH3 H2O—CH2Cl2) afforded the title compound (80 mg, 56%) as a white foam.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additiondiluted with ethyl acetate
  3. washwashed with NH4Cl (aq), NaCl (aq)
  4. dry with materialdried (MgSO4)
  5. customEvaporation of the solvent and purification of the residue by flash chromatography on silica gel (1:1:98 CH3OH—NH3 H2O—CH2Cl2)

Sources & evidence

ORD record
ord-b053ebfe8a5b49e5b420c3fa2924d00e
Source dataset
uspto-grants-2004_12
Patent number
US06835731B2

Reaction notes

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