Acetic Acid → Ethyl 2-{7-(benzyloxy)-5-[4-(methylsulfonyl)phenoxy]-1H-indol-2-yl}-1,3-thiazole-5-carboxylate

HRID 1188987Notes

Reaction equation

HRID 1188987 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([O:21][C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][CH:23]=2)[CH:12]=[C:13]2[C:17]=1[NH:16][C:15]([C:18](=[S:20])[NH2:19])=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[K].Cl[CH:34]([CH:40]=O)[C:35]([O:37][CH2:38][CH3:39])=[O:36].C(O)(=O)C.CN(C)C(=O)C>O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([O:21][C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][CH:23]=2)[CH:12]=[C:13]2[C:17]=1[NH:16][C:15]([C:18]1[S:20][C:34]([C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:40][N:19]=1)=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic Acid3×HCID 31374DimethylacetamideHCID 86623935Ethyl 2-chloro-3-oxopropanoate potassium salt3×HCID 866528577-(benzyloxy)-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carbothioamide

Product 1

HCID 66897604Ethyl 2-{7-(benzyloxy)-5-[4-(methylsulfonyl)phenoxy]-1H-indol-2-yl}-1,3-thiazole-5-carboxylateYield 71.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 7-(benzyloxy)-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carbothioamide (280 mg), ethyl 2-chloro-3-oxopropanoate potassium salt (234 mg), acetic acid (0.5 mL) and N,N-dimethylacetamide (5 mL) was stirred at 100° C. for 4 h. Ethyl 2-chloro-3-oxopropanoate potassium salt (234 mg) and acetic acid (0.5 mL) were added again, and the mixture was stirred at 100° C. for 3 h. Furthermore, ethyl 2-chloro-3-oxopropanoate potassium salt (234 mg) and acetic acid (0.5 mL) were added and the mixture was stirred at 100° C. for 7 h. Water was added to the mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=5/95 to 50/50, volume ratio) to give the title compound (242 mg, crude yield 71%) as a yellow solid. MS 549 (MH+).

Workup

  1. stirringthe mixture was stirred at 100° C. for 3 h
  2. stirringthe mixture was stirred at 100° C. for 7 h
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane=5/95 to 50/50, volume ratio)

Sources & evidence

ORD record
ord-120143478462464e92dcb0ca20f6eb2b
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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