Water → 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid

HRID 18521

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

30 mg (0.058 mmol) 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid methyl ester were dissolved in 3 mL dichloromethane and cooled to 0° C. 234 μl of a 1 M BBr3-solution (4 equiv.) in dichloromethane were carefully added and the resulting mixture was stirred at room temperature for 16 h. Under cooling 3 mL water were added dropwise followed by the addition of 0.7 mL of a 1 M NaOH-solution. The mixture was concentrated under reduced pressure. Purification by preparative HPLC (CH3CN/H2O gradient+0.05% formic acid) gave pure 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid. The corresponding dihydrochloride was obtained by treatment of the product with a 0.1 M HCl-solution and following lyophilization. Yield: 26 mg MS (ES+): m/e=499, chloro pattern.

Workup

additionwere added dropwise
concentrationThe mixture was concentrated under reduced pressure
customPurification by preparative HPLC (CH3CN/H2O gradient+0.05% formic acid)

Sources & evidence

ORD record: ord-ce88431b1b9040a59328fd962a121943
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07741341B2

Linked notes

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