1,3-Dichloroacetone → 7-chloro-3-[4-(chloromethyl)thiazol-2-yl]-1-(cyclohexyl)methyl-1H-indole

HRID 2358460Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)[CH:8]=[C:7]2[C:18](=[S:20])[NH2:19].[Cl:21][CH2:22][C:23]([CH2:25]Cl)=O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)[CH:8]=[C:7]2[C:18]1[S:20][CH:25]=[C:23]([CH2:22][Cl:21])[N:19]=1

Participants

Conditions

Temperature: 40 °C

Procedure

A mixture of 7-chloro-1-(cyclohexyl)methyl-1H-indole-3-carboxylic acid amide (1.74 g, 6.0 mmol), Lawesson's reagent (4.85 g, 12.0 mmol), toluene (150 ml) and tetrahydrofuran (50 ml) was stirred at room temperature for 3 days. The reaction mixture was concentrated in vacuo and the obtained reside was purified by column chromatography eluting with 20-50% (v/v) ethyl acetate in n-heptane to afford 7-chloro-1-(cyclohexyl)methyl-1H-indole-3-carbothioic acid amide (1.38 g, 4.50 mmol). A mixture of 7-chloro-1-(cyclohexyl)methyl-1H-indole-3-carbothioic acid amide (921 mg, 3.00 mmol), 1,3-dichloroacetone (571 mg, 4.50 mmol) in toluene (30 ml) was stirred at 40° C. for 18 h. The reaction mixture was concentrated in vacuo, and the obtained crystals were washed with 10% dichloromethane (v/v) in n-heptane to give 7-chloro-3-[4-(chloromethyl)thiazol-2-yl]-1-(cyclohexyl)methyl-1H-indole (587 mg, 1.55 mmol).

Workup

concentrationThe reaction mixture was concentrated in vacuo
washthe obtained crystals were washed with 10% dichloromethane (v/v) in n-heptane

Sources & evidence

ORD record: ord-57d15b3e51954ad894f74ee37a51fdec
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07763732B2

Reaction notes

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