Tributylphosphine → ethyl {2-[7-[methyl(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetate

HRID 504901Notes

Reaction equation

HRID 504901 reaction equation
[CH3:1][N:2]([S:20]([C:23]1[S:24][CH:25]=[CH:26][CH:27]=1)(=[O:22])=[O:21])[C:3]1[CH:4]=[C:5]([O:15][C:16]([F:19])([F:18])[F:17])[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]([NH2:14])=O)=[CH:8]2.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:37])=CC=1.[C:50]([O:55][CH2:56][CH3:57])(=[O:54])[C:51]#[C:52][CH3:53].C(P(CCCC)CCCC)CCC>O1CCCC1.C1(C)C=CC=CC=1>[CH3:1][N:2]([S:20]([C:23]1[S:24][CH:25]=[CH:26][CH:27]=1)(=[O:22])=[O:21])[C:3]1[CH:4]=[C:5]([O:15][C:16]([F:17])([F:19])[F:18])[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:37][CH:52]([CH2:51][C:50]([O:55][CH2:56][CH3:57])=[O:54])[CH2:53][N:14]=1)=[CH:8]2

Participants

7

Reactant 4

HCID 13831Tributylphosphine2×HCID 78043Ethyl 2-butynoate2×HCID 87949Lawesson's reagentHCID 574761877-[methyl(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indole-2-carboxamide

Product 1

HCID 57476345ethyl {2-[7-[methyl(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetateYield 41%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

A mixture of 7-[methyl(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indole-2-carboxamide (1.15 g), Lawesson's reagent (1.09 g) and tetrahydrofuran (20 mL) was stirred at 50° C. for 30 min. The reaction mixture was concentrated, and the residue was washed with diisopropyl ether to give pale-yellow crystals. A mixture of the obtained crystals, ethyl but-2-ynoate (710 mg), tributylphosphine (510 mg), toluene (30 mL) and tetrahydrofuran (15 mL) was stirred at 50° C. for 2 hr. ethyl but-2-ynoate (710 mg) and tributylphosphine (510 mg) were added to the mixture, and the mixture was further stirred at room temperature for 2.5 days. The reaction mixture was concentrated, and the residue was subjected to silica gel column chromatography, and eluted with hexane-ethyl acetate (4:1-3:1, volume ratio). The obtained crystals were washed with hexane to give the title compound (600 mg, yield 41%) as pale-yellow crystals. melting point 93-94° C.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. washthe residue was washed with diisopropyl ether
  3. customto give pale-yellow crystals
  4. stirringwas stirred at 50° C. for 2 hr
  5. stirringthe mixture was further stirred at room temperature for 2.5 days
  6. concentrationThe reaction mixture was concentrated
  7. washeluted with hexane-ethyl acetate (4:1-3:1, volume ratio)
  8. washThe obtained crystals were washed with hexane

Sources & evidence

ORD record
ord-0aca05c6a79549a49ccac009b03dd9c2
Source dataset
uspto-grants-2010_08
Patent number
US07777047B2

Reaction notes

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