2-(4-Chlorophenyl)ethyl chloride → 1-[2-(4-Chloro-phenyl)-ethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid methyl ester

HRID 18569Notes

Reaction equation

HRID 18569 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:25]=[CH:24][C:8]2[NH:9][C:10]([C:12](=[O:23])[NH:13][CH:14]3[CH2:19][CH2:18][N:17]([CH:20]([CH3:22])[CH3:21])[CH2:16][CH2:15]3)=[N:11][C:7]=2[CH:6]=1)=[O:4].[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][CH2:34]Cl)=[CH:29][CH:28]=1.CC#N.O>C(O)=O>[CH3:1][O:2][C:3]([C:5]1[CH:25]=[CH:24][C:8]2[N:9]([CH2:34][CH2:33][C:30]3[CH:31]=[CH:32][C:27]([Cl:26])=[CH:28][CH:29]=3)[C:10]([C:12](=[O:23])[NH:13][CH:14]3[CH2:19][CH2:18][N:17]([CH:20]([CH3:22])[CH3:21])[CH2:16][CH2:15]3)=[N:11][C:7]=2[CH:6]=1)=[O:4].[CH3:1][O:2][C:3]([C:5]1[CH:25]=[CH:24][C:8]2[N:9]=[C:10]([C:12](=[O:23])[NH:13][CH:14]3[CH2:19][CH2:18][N:17]([CH:20]([CH3:22])[CH3:21])[CH2:16][CH2:15]3)[N:11]([CH2:34][CH2:33][C:30]3[CH:31]=[CH:32][C:27]([Cl:26])=[CH:28][CH:29]=3)[C:7]=2[CH:6]=1)=[O:4]

Participants

6

Reactant 3

HCID 37903592-(4-Chlorophenyl)ethyl chloride2×HCID 18373917Acetonitrile--water (1/1)HCID 178497373HCID 178497373, compound

Product 2

HCID 670119401-[2-(4-Chloro-phenyl)-ethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid methyl esterHCID 670121053-[2-(4-Chloro-phenyl)-ethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-3H-benzoimidazole-5-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

1-[2-(4-Chloro-phenyl)-ethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid methyl ester and 3-[2-(4-Chloro-phenyl)-ethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-3H-benzoimidazole-5-carboxylic acid methyl ester were prepared by a procedure according to example 5 iii) starting from 300 mg (0.87 mmol) 2-(1-Isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid methyl ester and 365.9 mg (2.09 mmol) 1-chloro-4-(2-chloro-ethyl)-benzene. Since 1-chloro-4-(2-chloro-ethyl)-benzene is less reactive the reaction time had to be extended to 10 h. Preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid) gave a 4:3 mixture of both isomers described in the title. These isomers could be separated by NP-HPLC using a chiral stationary phase and a mixture of heptane, ethanol and methanol as solvent. Structural assignment of both isomers was achieved by NOE-spectroscopy.

Workup

  1. additiona 4:3 mixture of both isomers
  2. customThese isomers could be separated by NP-HPLC
  3. additiona mixture of heptane, ethanol and methanol as solvent

Sources & evidence

ORD record
ord-0317c31ca552429b8b2f56cbe46f58a2
Source dataset
uspto-grants-2010_06
Patent number
US07741341B2

Reaction notes

Loading…