Acetonitrile--water (1/1) → 3-[5-(5-Chloro-thiophen-2-yl)-[1,3,4]thiadiazol-2-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-3H-benzoimidazole-5-carboxylic acid

HRID 18595Notes

Reaction equation

HRID 18595 reaction equation
C[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].Br[CH2:27][C:28]1[S:29][C:30]([C:33]2[S:34][C:35]([Cl:38])=[CH:36][CH:37]=2)=[N:31][N:32]=1.CC#N.O>C(O)=O>[Cl:38][C:35]1[S:34][C:33]([C:30]2[S:29][C:28]([CH2:27][N:9]3[C:8]4[CH:24]=[CH:25][C:5]([C:3]([OH:2])=[O:4])=[CH:6][C:7]=4[N:11]=[C:10]3[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:32][N:31]=2)=[CH:37][CH:36]=1.[Cl:38][C:35]1[S:34][C:33]([C:30]2[S:29][C:28]([CH2:27][N:11]3[C:7]4[CH:6]=[C:5]([C:3]([OH:2])=[O:4])[CH:25]=[CH:24][C:8]=4[N:9]=[C:10]3[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:32][N:31]=2)=[CH:37][CH:36]=1

Participants

6

Reactant 3

HCID 18373917Acetonitrile--water (1/1)HCID 223944202-Bromomethyl-5-(5-chloro-thiophen-2-yl)-[1,3,4]thiadiazoleHCID 178497372HCID 178497372, compound

Product 2

HCID 686151993-[5-(5-Chloro-thiophen-2-yl)-[1,3,4]thiadiazol-2-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-3H-benzoimidazole-5-carboxylic acidHCID 686152761-[5-(5-Chloro-thiophen-2-yl)-[1,3,4]thiadiazol-2-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

1-[5-(5-Chloro-thiophen-2-yl)-[1,3,4]thiadiazol-2-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid and 3-[5-(5-Chloro-thiophen-2-yl)-[1,3,4]thiadiazol-2-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-3H-benzoimidazole-5-carboxylic acid were prepared by a procedure according to example 81 starting from 200 mg (0.58 mmol) 2-(1-Cyclopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid methyl ester and 181.8 mg (0.58 mmol) 2-bromomethyl-5-(5-chloro-thiophen-2-yl)-[1,3,4]thiadiazole. Hydrolysis of the resulting esters 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.

Sources & evidence

ORD record
ord-d833326bfc5840658dc96d91537ecd6d
Source dataset
uspto-grants-2010_06
Patent number
US07741341B2

Reaction notes

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