1,3-Dichloroacetone → HCID 68697908, compound

HRID 644037Notes

Reaction equation

HRID 644037 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](=[S:21])[NH2:20])=[CH:9]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:22][CH2:23][C:24]([CH2:26]Cl)=O>C(O)C>[Cl:22][CH2:23][C:24]1[N:20]=[C:19]([C:10]2[C:11]3[C:16](=[C:15]([O:17][CH3:18])[CH:14]=[CH:13][CH:12]=3)[N:8]([CH2:7][CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)[CH:9]=2)[S:21][CH:26]=1

Participants

4

Reactant 2

HCID 107931,3-DichloroacetoneHCID 860732681-(cyclohexyl)methyl-7-methoxy-1H-indole-3-carbothioic acid amide

Product 1

HCID 68697908HCID 68697908, compoundYield 80.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

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. additionthe obtained residue was mixed with 5% aqueous sodium carbonate (100 ml)
  3. extractionThe resulting mixture was extracted with dichloromethane (4×100 ml)
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe obtained residue was purified by column chromatography
  8. washeluting with 25% (v/v) ethyl acetate in n-heptane

Sources & evidence

ORD record
ord-1ae6691c832648b89a76fe0778cbdf07
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

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