Lawesson's reagent → 1-(cyclohexyl)methyl-7-methoxy-1H-indole-3-carbothioic acid amide

HRID 644036Notes

Reaction equation

HRID 644036 reaction equation
[CH:1]1([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[O:17][CH3:18])[C:10]([C:19]([NH2:21])=O)=[CH:9]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:31])=CC=1>C1(C)C=CC=CC=1>[CH:1]1([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[O:17][CH3:18])[C:10]([C:19](=[S:31])[NH2:21])=[CH:9]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 87949Lawesson's reagentHCID 68697465HCID 68697465, compound

Product 1

HCID 860732681-(cyclohexyl)methyl-7-methoxy-1H-indole-3-carbothioic acid amideYield 66.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 1-(cyclohexyl)methyl-7-methoxy-1H-indole-3-carboxylic acid amide (prepared from 7-methoxyindole as described in Example 1; 5.10 g, 17.8 mmol), Lawesson's reagent (7.92 g, 19.6 mmol), and toluene (150 ml) was stirred at room temperature for 4 days. The reaction mixture was concentrated in vacuo and the obtained reside was purified by column chromatography eluting with dichloromethane to afford 1-(cyclohexyl)methyl-7-methoxy-1H-indole-3-carbothioic acid amide (3.58 g). A mixture of 1-(cyclohexyl)methyl-7-methoxy-1H-indole-3-carbothioic acid amide (200 mg, 0.66 mmol), 1,3-dichloroacetone (126 mg, 0.99 mmol), and ethanol (2.0 ml) was stirred at 60° C. for 1 h. The reaction mixture was concentrated in vacuo, and the obtained residue was mixed with 5% aqueous sodium carbonate (100 ml). The resulting mixture was extracted with dichloromethane (4×100 ml). The organic layers were combined, washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The obtained residue was purified by column chromatography eluting with 25% (v/v) ethyl acetate in n-heptane to give 3-[4-(chloromethyl)thiazol-2-yl]-1-(cyclohexyl)methyl-7-methoxy-1H-indole (200 mg).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe obtained reside was purified by column chromatography
  3. washeluting with dichloromethane

Sources & evidence

ORD record
ord-9516d3e3e09c4b389ebce865a7db1857
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

Loading…