Potassium Carbonate → 3-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-3H-benzoimidazole-5-carboxylic acid methyl ester

HRID 18577Notes

Reaction equation

HRID 18577 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]4[CH2:22][CH2:21]4)[CH2:16][CH2:15]3)=[N:11][C:7]=2[CH:6]=1)=[O:4].C([O-])([O-])=O.[K+].[K+].[Cl:32][C:33]1[S:37][C:36]([C:38]2[O:42][N:41]=[C:40]([CH2:43]OS(C)(=O)=O)[CH:39]=2)=[CH:35][CH:34]=1>CN(C=O)C>[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[CH2:15][CH2:16][N:17]([CH:20]4[CH2:22][CH2:21]4)[CH2:18][CH2:19]3)[N:11]([CH2:43][C:40]3[CH:39]=[C:38]([C:36]4[S:37][C:33]([Cl:32])=[CH:34][CH:35]=4)[O:42][N:41]=3)[C:7]=2[CH:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 865958785-(5-Chlorothiophen-2-yl)isoxazol-3-ylmethyl methanesulfonateHCID 178497372HCID 178497372, compound

Product 1

HCID 670117253-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-3H-benzoimidazole-5-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

17.3 g (50.52 mmol) 2-(1-Cyclopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid methyl ester were dissolved in 800 mL DMF. Subsequently 10.47 g (75.8 mmol) K2CO3 and 14.84 g (50.52 mmol) methanesulfonic acid 5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl ester were added and the resulting mixture was stirred for 2 h at 80° C. The mixture was concentrated under reduced pressure. The residue was suspended in 800 mL ethyl acetate. The next day the resulting precipitate was filtered off and washed with 100 mL ethyl acetate to give 3-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-3H-benzoimidazole-5-carboxylic acid methyl ester. The filtrate was concentrated to a volume of approx. 100 mL. Again the formed precipitate was filtered off. That procedure was repeated once again. The remaining filtrate was concentrated under reduced pressure and finally purified by flash-chromatography on silica gel using ethyl acetate as eluent. The product containing fractions were concentrated under vacuo to give pure (>98%) 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid methyl ester as a light brown crystalline solid.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. filtrationThe next day the resulting precipitate was filtered off
  3. washwashed with 100 mL ethyl acetate

Sources & evidence

ORD record
ord-539ee90945854d658e7a37df7d6e73b7
Source dataset
uspto-grants-2010_06
Patent number
US07741341B2

Reaction notes

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