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

HRID 1995012Notes

Reaction equation

HRID 1995012 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[C:13]([N:15]([CH3:24])[S:16]([C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)(=[O:18])=[O:17])[CH:14]=1)[NH:11][C:10]([C:25]([NH2:27])=O)=[CH:9]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][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[C:13]([N:15]([CH3:24])[S:16]([C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)(=[O:18])=[O:17])[CH:14]=1)[NH:11][C:10]([C:25]1[S:37][CH:52]([CH2:51][C:50]([O:55][CH2:56][CH3:57])=[O:54])[CH2:53][N:27]=1)=[CH:9]2

Participants

7

Reactant 4

HCID 13831TributylphosphineHCID 78043Ethyl 2-butynoateHCID 87949Lawesson's reagentHCID 574761955-(2-methoxyethoxy)-7-[methyl(2-thienylsulfonyl)amino]-1H-indole-2-carboxamide

Product 1

HCID 59303535ethyl(2-{5-(2-methoxyethoxy)-7-[methyl(2-thienylsulfonyl)amino]-1H-indol-2-yl}-4,5-dihydro-1,3-thiazol-5-yl)acetateYield 54.5%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

A mixture of 5-(2-methoxyethoxy)-7-[methyl(2-thienylsulfonyl)amino]-1H-indole-2-carboxamide (920 mg), Lawesson's reagent (690 mg) and tetrahydrofuran (20 mL) was stirred at 50° C. for 2 hr. The reaction mixture was concentrated, and the residue was subjected to silica gel column chromatography, and eluted with hexane-ethyl acetate (2:1-1:9, volume ratio) to give a yellow amorphous solid. A mixture of the obtained amorphous solid, ethyl but-2-ynoate (620 mg), tributylphosphine (450 mg), toluene (30 mL) and tetrahydrofuran (15 mL) was stirred at 50° C. for 1 hr. The reaction mixture was concentrated, and the residue was subjected to silica gel column chromatography, and eluted with hexane-ethyl acetate (4:1-1:1, volume ratio). The obtained compound was further subjected to silica gel column chromatography, and eluted with hexane-ethyl acetate (1:1, volume ratio) to give the title compound (500 mg, yield 42%) as a yellow oil

Workup

  1. concentrationThe reaction mixture was concentrated
  2. washeluted with hexane-ethyl acetate (2:1-1:9, volume ratio)
  3. customto give a yellow amorphous solid
  4. stirringwas stirred at 50° C. for 1 hr
  5. concentrationThe reaction mixture was concentrated
  6. washeluted with hexane-ethyl acetate (4:1-1:1, volume ratio)
  7. washeluted with hexane-ethyl acetate (1:1, volume ratio)

Sources & evidence

ORD record
ord-f4ca64cf60d64db98f38e27d5afe9f38
Source dataset
uspto-grants-2010_01
Patent number
US07652133B2

Reaction notes

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