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

HRID 1995011Notes

Reaction equation

HRID 1995011 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6]([NH:9][C:10]1[CH:11]=[C:12]([O:22][C:23]([F:26])([F:25])[F:24])[CH:13]=[C:14]2[C:18]=1[NH:17][C:16]([C:19]([NH2:21])=O)=[CH:15]2)(=[O:8])=[O:7].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:36])=CC=1.[C:49]([O:54][CH2:55][CH3:56])(=[O:53])[C:50]#[C:51][CH3:52].C(P(CCCC)CCCC)CCC>O1CCCC1.C1(C)C=CC=CC=1>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6]([NH:9][C:10]1[CH:11]=[C:12]([O:22][C:23]([F:24])([F:25])[F:26])[CH:13]=[C:14]2[C:18]=1[NH:17][C:16]([C:19]1[S:36][CH:51]([CH2:50][C:49]([O:54][CH2:55][CH3:56])=[O:53])[CH2:52][N:21]=1)=[CH:15]2)(=[O:8])=[O:7]

Participants

7

Reactant 4

HCID 13831Tributylphosphine2×HCID 78043Ethyl 2-butynoate2×HCID 87949Lawesson's reagentHCID 574764287-[(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indole-2-carboxamide

Product 1

HCID 57476351ethyl{2-(7-[(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetateYield 28%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

A mixture of 7-[(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indole-2-carboxamide (2.14 g), Lawesson's reagent (2.14 g) and tetrahydrofuran (50 mL) was stirred at 50° C. for 1.5 hr, and heated under reflux for 1.5 hr. The reaction mixture was concentrated, and the residue was washed with diisopropyl ether to give pale-yellow crystals. The obtained crystals were subjected to silica gel column chromatography, and eluted with hexane-ethyl acetate (4:1-1:2, volume ratio) to give yellow crystals. A mixture of the obtained crystals, ethyl but-2-ynoate (1.49 g), tributylphosphine (1.07 g), toluene (30 mL) and tetrahydrofuran (10 mL) was stirred at 70° C. for 5 hr. ethyl but-2-ynoate (900 mg) and tributylphosphine (1.07 g) 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 (4:1-1:3, volume ratio) to give the title compound (780 mg, yield 28%) as a brown oil.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 1.5 hr
  3. concentrationThe reaction mixture was concentrated
  4. washthe residue was washed with diisopropyl ether
  5. customto give pale-yellow crystals
  6. washeluted with hexane-ethyl acetate (4:1-1:2, volume ratio)
  7. customto give yellow crystals
  8. stirringwas stirred at 70° C. for 5 hr
  9. stirringthe mixture was further stirred at room temperature for 2.5 days
  10. concentrationThe reaction mixture was concentrated
  11. washeluted with hexane-ethyl acetate (4:1-1:3, volume ratio)

Sources & evidence

ORD record
ord-12e841ca5a9b48e1b85d0c6964ce43fa
Source dataset
uspto-grants-2010_01
Patent number
US07652133B2

Reaction notes

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