Boron tribromide → 3-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-3H-thieno[3,4-d]imidazole-6-carboxylic acid

HRID 18590

Reaction equation

HRID 18590 reaction equation
C[O:2][C:3]([C:5]1[S:6][CH:7]=[C:8]2[NH:12][C:11]([C:13](=[O:24])[NH:14][CH:15]3[CH2:20][CH2:19][N:18]([CH:21]([CH3:23])[CH3:22])[CH2:17][CH2:16]3)=[N:10][C:9]=12)=[O:4].Br[CH2:26][C:27]([NH:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][N:31]=1)=[O:28].B(Br)(Br)Br>>[Cl:36][C:33]1[CH:34]=[CH:35][C:30]([NH:29][C:27]([CH2:26][N:12]2[C:8]3=[CH:7][S:6][C:5]([C:3]([OH:2])=[O:4])=[C:9]3[N:10]=[C:11]2[C:13](=[O:24])[NH:14][CH:15]2[CH2:20][CH2:19][N:18]([CH:21]([CH3:23])[CH3:22])[CH2:17][CH2:16]2)=[O:28])=[N:31][CH:32]=1.[Cl:36][C:33]1[CH:34]=[CH:35][C:30]([NH:29][C:27]([CH2:26][N:10]2[C:9]3=[C:5]([C:3]([OH:2])=[O:4])[S:6][CH:7]=[C:8]3[N:12]=[C:11]2[C:13](=[O:24])[NH:14][CH:15]2[CH2:20][CH2:19][N:18]([CH:21]([CH3:22])[CH3:23])[CH2:17][CH2:16]2)=[O:28])=[N:31][CH:32]=1

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 34211102-Bromo-N-(5-chloro-2-pyridinyl)acetamideHCID 686161172-(1-isopropyl-piperidin-4-ylcarbamoyl)-3H-thieno[3,4-d]imidazole-6-carboxylic acid methyl ester

Product 2

HCID 670115813-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-3H-thieno[3,4-d]imidazole-6-carboxylic acidHCID 670119573-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-3H-thieno[3,4-d]imidazole-4-carboxylic acid

Procedure

3-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-3H-thieno[3,4-d]imidazole-6-carboxylic acid and 3-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-3H-thieno[3,4-d]imidazole-4-carboxylic acid were prepared by a procedure according to example 81 starting from 500 mg (1.40 mmol) 2-(1-isopropyl-piperidin-4-ylcarbamoyl)-3H-thieno[3,4-d]imidazole-6-carboxylic acid methyl ester and 356.0 mg (1.40 mmol) 2-bromo-N-(5-chloro-pyridin-2-yl)-acetamide. Hydrolysis of the resulting esters by treatment with BBr3 according to example 16 and purification by preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid) gave the title compounds as their formiates in form of white amorphous solids. Structural assignment of both isomers was achieved by NOE-spectroscopy.

Workup

  1. customto example 16 and purification by preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid)

Sources & evidence

ORD record
ord-088002c79bbe41069276d61631ba32fe
Source dataset
uspto-grants-2010_06
Patent number
US07741341B2

Linked notes

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