5-Fluoro-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid ethyl ester → 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-fluoro-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid

HRID 18614Notes

Reaction equation

HRID 18614 reaction equation
C([O:3][C:4]([C:6]1[C:14]2[N:13]=[C:12]([C:15](=[O:26])[NH:16][CH:17]3[CH2:22][CH2:21][N:20]([CH:23]([CH3:25])[CH3:24])[CH2:19][CH2:18]3)[NH:11][C:10]=2[CH:9]=[CH:8][C:7]=1[F:27])=[O:5])C.[Cl:28][C:29]1[S:33][C:32]([C:34]2[O:38][N:37]=[C:36]([CH2:39]OS(C)(=O)=O)[CH:35]=2)=[CH:31][CH:30]=1>>[Cl:28][C:29]1[S:33][C:32]([C:34]2[O:38][N:37]=[C:36]([CH2:39][N:11]3[C:10]4[CH:9]=[CH:8][C:7]([F:27])=[C:6]([C:4]([OH:3])=[O:5])[C:14]=4[N:13]=[C:12]3[C:15](=[O:26])[NH:16][CH:17]3[CH2:18][CH2:19][N:20]([CH:23]([CH3:24])[CH3:25])[CH2:21][CH2:22]3)[CH:35]=2)=[CH:31][CH:30]=1

Participants

3

Reactant 2

HCID 686165615-Fluoro-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid ethyl esterHCID 865958785-(5-Chlorothiophen-2-yl)isoxazol-3-ylmethyl methanesulfonate

Product 1

HCID 670125291-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-fluoro-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid

Procedure

1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-fluoro-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid was prepared by a procedure according to example 81 starting from 230 mg (0.60 mmol) 5-Fluoro-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid ethyl ester and 179.5 mg (0.60 mmol) methanesulfonic acid 5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl ester. Hydrolysis of the resulting ethyl ester by treatment with LiOH and purification by preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid) gave the title compound as its formiate in form of a white amorphous solid.

Workup

  1. custom1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-fluoro-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid was prepared by a procedure
  2. customwith LiOH and purification by preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid)

Sources & evidence

ORD record
ord-4daa0075bca94a34a3f4101fea6a7eff
Source dataset
uspto-grants-2010_06
Patent number
US07741341B2

Reaction notes

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