3-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole → 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid

HRID 18584Notes

Reaction equation

HRID 18584 reaction equation
C[O:2][C:3]([C:5]1[C:13]2[N:12]=[C:11]([C:14](=[O:25])[NH:15][CH:16]3[CH2:21][CH2:20][N:19]([CH:22]4[CH2:24][CH2:23]4)[CH2:18][CH2:17]3)[NH:10][C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4].Br[CH2:27][C:28]1[CH:32]=[C:31]([C:33]2[S:34][C:35]([Cl:38])=[CH:36][CH:37]=2)[O:30][N:29]=1.CC#N.O>C(O)=O>[Cl:38][C:35]1[S:34][C:33]([C:31]2[O:30][N:29]=[C:28]([CH2:27][N:10]3[C:9]4[CH:8]=[CH:7][CH:6]=[C:5]([C:3]([OH:2])=[O:4])[C:13]=4[N:12]=[C:11]3[C:14](=[O:25])[NH:15][CH:16]3[CH2:17][CH2:18][N:19]([CH:22]4[CH2:23][CH2:24]4)[CH2:20][CH2:21]3)[CH:32]=2)=[CH:37][CH:36]=1.[Cl:38][C:35]1[S:34][C:33]([C:31]2[O:30][N:29]=[C:28]([CH2:27][N:12]3[C:13]4[C:5]([C:3]([OH:2])=[O:4])=[CH:6][CH:7]=[CH:8][C:9]=4[N:10]=[C:11]3[C:14](=[O:25])[NH:15][CH:16]3[CH2:17][CH2:18][N:19]([CH:22]4[CH2:23][CH2:24]4)[CH2:20][CH2:21]3)[CH:32]=2)=[CH:37][CH:36]=1

Participants

6

Reactant 3

HCID 111501463-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazoleHCID 18373917Acetonitrile--water (1/1)HCID 686165452-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid methyl ester

Product 2

HCID 670113361-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acidHCID 670118833-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-3H-benzoimidazole-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid and 3-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-3H-benzoimidazole-4-carboxylic acid were prepared by a procedure according to example 81 starting from 248.0 mg (0.72 mmol) 2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid methyl ester and 221.9 mg (0.79 mmol) 3-bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole. Hydrolysis of the resulting esters and purification by preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid) gave the title compounds as their formiates in form of white amorphous solids. The corresponding hydrochlorides were obtained by treatment of both products with a 0.1 M HCl-solution and following lyophilization. Yield of 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid: 119 mg MS (ES+): m/e=526, chloro pattern.

Sources & evidence

ORD record
ord-3db637a320754d87966a5d8f561e1150
Source dataset
uspto-grants-2010_06
Patent number
US07741341B2

Reaction notes

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