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

HRID 18616Notes

Reaction equation

HRID 18616 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[O:27][CH2:28][C:29]([F:32])([F:31])[F:30])=[O:5])C.[Cl:33][C:34]1[S:38][C:37]([C:39]2[O:43][N:42]=[C:41]([CH2:44]OS(C)(=O)=O)[CH:40]=2)=[CH:36][CH:35]=1>>[Cl:33][C:34]1[S:38][C:37]([C:39]2[O:43][N:42]=[C:41]([CH2:44][N:11]3[C:10]4[CH:9]=[CH:8][C:7]([O:27][CH2:28][C:29]([F:32])([F:31])[F:30])=[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[CH2:22][CH2:21][N:20]([CH:23]([CH3:24])[CH3:25])[CH2:19][CH2:18]3)[CH:40]=2)=[CH:36][CH:35]=1

Participants

3

Reactant 2

HCID 686161102-(1-Isopropyl-piperidin-4-ylcarbamoyl)-5-(2,2,2-trifluoro-ethoxy)-1H-benzoimidazole-4-carboxylic acid ethyl esterHCID 865958785-(5-Chlorothiophen-2-yl)isoxazol-3-ylmethyl methanesulfonate

Product 1

HCID 670113761-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-5-(2,2,2-trifluoro-ethoxy)-1H-benzoimidazole-4-carboxylic acid

Procedure

1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-5-(2,2,2-trifluoro-ethoxy)-1H-benzoimidazole-4-carboxylic acid was prepared by a procedure according to example 81 starting from 299.0 mg (0.66 mmol) 2-(1-Isopropyl-piperidin-4-ylcarbamoyl)-5-(2,2,2-trifluoro-ethoxy)-1H-benzoimidazole-4-carboxylic acid ethyl ester and 192.4 mg (0.66 mmol) methanesulfonic acid 5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl ester. Hydrolysis of the resulting ethyl ester by treatment with LiOH in MeOH 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. Yield: 90 mg MS (ES+): m/e=626, chloro pattern.

Workup

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

Sources & evidence

ORD record
ord-e83092589ca345b0ac957e5b77cd781e
Source dataset
uspto-grants-2010_06
Patent number
US07741341B2

Reaction notes

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