Diisopropylethylamine → 3-{4-[4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-propionitrile

HRID 31514Notes

Reaction equation

HRID 31514 reaction equation
Br[CH:2]([CH3:5])[C:3]#[N:4].Cl.[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]2[CH:18]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=3)[N:17]([C:26]([N:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)=[O:27])[C:16]([C:34]3[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:36][C:35]=3[O:44][CH2:45][CH3:46])=[N:15]2)=[CH:10][CH:9]=1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([CH:14]2[CH:18]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=3)[N:17]([C:26]([N:28]3[CH2:33][CH2:32][N:31]([CH2:5][CH2:2][C:3]#[N:4])[CH2:30][CH2:29]3)=[O:27])[C:16]([C:34]3[CH:39]=[CH:38][C:37]([C:40]([F:41])([F:43])[F:42])=[CH:36][C:35]=3[O:44][CH2:45][CH3:46])=[N:15]2)=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1405382-BromopropionitrileHCID 86595528[4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-(piperazin-1-yl)-methanone hydrochloride

Product 1

HCID 111815003-{4-[4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-propionitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Bromopropionitrile (10 uL, 0.120 mmol) was added to a mixture of [4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-[piperazin-1-yl]-methanone hydrochloride and diisopropylethylamine (42 uL, 0.240 mmol) in dimethylformamide (1.0 mL). The reaction was stirred at room temperature overnight. Evaporation of the solvent and purification of the crude residue by flash chromatography over silica gel using 1-2% methanol in methylene chloride gave 3-{4-[4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-propionitrile, which was dissolved in dilute hydrochloric acid (0.5 N, 1 mL) and lyophilized to give 3-{4-[4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-propionitrile hydrochloride as an off-white powder (20 mg, 39% yield). LR-MS (APCI): 644.4 [(M+H)+].

Workup

  1. customEvaporation of the solvent and purification of the crude residue by flash chromatography over silica gel using 1-2% methanol in methylene chloride

Sources & evidence

ORD record
ord-351c28caa80a42c4b0114a9bcfdce508
Source dataset
uspto-grants-2008_09
Patent number
US07425638B2

Reaction notes

Loading…