Hydrochloric Acid → 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid

HRID 18514Notes

Reaction equation

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

Participants

Conditions

Temperature: 60 °C

Procedure

To a suspension of 43.6 mg (0.080 mmol) 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid methyl ester in 4 mL MeOH 0.4 mL of a 1 M aqueous LiOH-solution were added and the resulting mixture was stirred at 60° C. for 5 h. The mixture was acidified by the addition of a 1 M HCl-solution (pH≈2-3) and concentrated under reduced pressure. Final purification by preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid) gave pure 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid. The corresponding dihydrochloride was obtained by treatment of the product with a 0.1 M HCl-solution followed by lyophilization. Yield: 43 mg MS (ES+): m/e=528, chloro pattern.

Workup

additionwere added
concentrationconcentrated under reduced pressure
customFinal purification by preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid)

Sources & evidence

ORD record: ord-2c6b00538d104f2bbb7346b2a580ab20
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07741341B2

Reaction notes

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