3-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole → 3-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-3H-thieno[3,4-d]imidazole-4-carboxylic acid

HRID 18587Notes

Reaction equation

HRID 18587 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]1[CH:31]=[C:30]([C:32]2[S:33][C:34]([Cl:37])=[CH:35][CH:36]=2)[O:29][N:28]=1.CC#N.O>C(O)=O>[Cl:37][C:34]1[S:33][C:32]([C:30]2[O:29][N:28]=[C:27]([CH2:26][N:12]3[C:8]4=[CH:7][S:6][C:5]([C:3]([OH:2])=[O:4])=[C:9]4[N:10]=[C:11]3[C:13](=[O:24])[NH:14][CH:15]3[CH2:16][CH2:17][N:18]([CH:21]([CH3:22])[CH3:23])[CH2:19][CH2:20]3)[CH:31]=2)=[CH:36][CH:35]=1.[Cl:37][C:34]1[S:33][C:32]([C:30]2[O:29][N:28]=[C:27]([CH2:26][N:10]3[C:9]4=[C:5]([C:3]([OH:2])=[O:4])[S:6][CH:7]=[C:8]4[N:12]=[C:11]3[C:13](=[O:24])[NH:14][CH:15]3[CH2:20][CH2:19][N:18]([CH:21]([CH3:22])[CH3:23])[CH2:17][CH2:16]3)[CH:31]=2)=[CH:36][CH:35]=1

Participants

6

Reactant 3

HCID 111501463-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazoleHCID 18373917Acetonitrile--water (1/1)HCID 686161172-(1-isopropyl-piperidin-4-ylcarbamoyl)-3H-thieno[3,4-d]imidazole-6-carboxylic acid methyl ester

Product 2

HCID 670114953-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-3H-thieno[3,4-d]imidazole-4-carboxylic acidHCID 670116223-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-3H-thieno[3,4-d]imidazole-6-carboxylic acid

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

3-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-3H-thieno[3,4-d]imidazole-6-carboxylic acid and 3-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-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 397.4 mg (1.40 mmol) 3-bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole. 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-72a32f8e5555411e84ae549bbec64a7c
Source dataset
uspto-grants-2010_06
Patent number
US07741341B2

Reaction notes

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