5-(5-Chlorothiophen-2-yl)isoxazol-3-ylmethyl methanesulfonate → HCID 67012730, compound

HRID 18612Notes

Reaction equation

HRID 18612 reaction equation
C[O:2][C:3]([C:5]1[CH:25]=[C:24]([CH3:26])[C:8]2[NH:9][C:10]([C:12](=[O:23])[NH:13][CH:14]3[CH2:19][CH2:18][N:17]([CH:20]4[CH2:22][CH2:21]4)[CH2:16][CH2:15]3)=[N:11][C:7]=2[CH:6]=1)=[O:4].[Cl:27][C:28]1[S:32][C:31]([C:33]2[O:37][N:36]=[C:35]([CH2:38]OS(C)(=O)=O)[CH:34]=2)=[CH:30][CH:29]=1>>[Cl:27][C:28]1[S:32][C:31]([C:33]2[O:37][N:36]=[C:35]([CH2:38][N:9]3[C:8]4[C:24]([CH3:26])=[CH:25][C:5]([C:3]([OH:2])=[O:4])=[CH:6][C:7]=4[N:11]=[C:10]3[C:12](=[O:23])[NH:13][CH:14]3[CH2:19][CH2:18][N:17]([CH:20]4[CH2:22][CH2:21]4)[CH2:16][CH2:15]3)[CH:34]=2)=[CH:30][CH:29]=1.[Cl:27][C:28]1[S:32][C:31]([C:33]2[O:37][N:36]=[C:35]([CH2:38][N:11]3[C:7]4[CH:6]=[C:5]([C:3]([OH:2])=[O:4])[CH:25]=[C:24]([CH3:26])[C:8]=4[N:9]=[C:10]3[C:12](=[O:23])[NH:13][CH:14]3[CH2:19][CH2:18][N:17]([CH:20]4[CH2:21][CH2:22]4)[CH2:16][CH2:15]3)[CH:34]=2)=[CH:30][CH:29]=1

Participants

4

Reactant 2

HCID 865958785-(5-Chlorothiophen-2-yl)isoxazol-3-ylmethyl methanesulfonateHCID 178497594HCID 178497594, compound

Product 2

HCID 67012730HCID 67012730, compoundHCID 686163231-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-7-methyl-1H-benzoimidazole-5-carboxylic acid

Procedure

1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-7-methyl-1H-benzoimidazole-5-carboxylic acid and 3-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-7-methyl-3H-benzoimidazole-5-carboxylic acid were prepared by a procedure according to example 81 starting from 200 mg (0.56 mmol) 2-(1-Cyclopropyl-piperidin-4-ylcarbamoyl)-7-methyl-1H-benzoimidazole-5-carboxylic acid methyl ester and 164.8 mg (0.56 mmol) methanesulfonic acid 5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl ester. Hydrolysis of the resulting esters by treatment with LiOH 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. Structural assignment of both isomers was achieved by NOE-spectroscopy.

Workup

  1. customwith LiOH and purification by preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid)

Sources & evidence

ORD record
ord-3ef71dcded8e4411acd2e6fd3e0c396f
Source dataset
uspto-grants-2010_06
Patent number
US07741341B2

Reaction notes

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