Tributylphosphine → HCID 70963867, compound

HRID 1189021Notes

Reaction equation

HRID 1189021 reaction equation
[CH3:1][O:2][CH2:3][C:4]1[N:9]=[CH:8][C:7]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[C:18]([O:20][CH:21]([CH3:23])[CH3:22])[CH:19]=2)[NH:16][C:15]([C:24]([NH2:26])=O)=[CH:14]3)=[CH:6][CH:5]=1.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>[CH3:1][O:2][CH2:3][C:4]1[N:9]=[CH:8][C:7]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[C:18]([O:20][CH:21]([CH3:22])[CH3:23])[CH:19]=2)[NH:16][C:15]([C:24]2[S:36][CH:51]([CH2:50][C:49]([O:54][CH2:55][CH3:56])=[O:53])[CH2:52][N:26]=2)=[CH:14]3)=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 13831Tributylphosphine2×HCID 78043Ethyl 2-butynoate2×HCID 87949Lawesson's reagentHCID 66897826HCID 66897826, compound

Product 1

HCID 70963867HCID 70963867, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

A mixture of 5-{[6-(methoxymethyl)pyridin-3-yl]oxy}-7-(1-methylethoxy)-1H-indole-2-carboxamide (1.0 g), Lawesson's reagent (1.25 g) and tetrahydrofuran (100 mL) was stirred at 70° C. for 2 h. The mixture was concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate:hexane=1:9 to 1:1) to give a yellow amorphous solid. A mixture of the solid, ethyl 2-butynoate (0.78 g), tributylphosphine (565 mg) and tetrahydrofuran (50 mL) was refluxed for 15 h, and then ethyl 2-butynoate (0.78 g) and tributylphosphine (565 mg) were added to the mixture. The whole was refluxed for further 30 min, and then concentrated in vacuo. The residue was purified by basic silica gel chromatography (ethyl acetate:hexane=1:9 to 1:1, volume ratio) and then by silica gel chromatography (ethyl acetate:hexane=1:9 to 2:1) to give the title compound (0.68 g, 50%) as a yellow oil. MS 484 (MH+).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customThe residue was purified by silica gel chromatography (ethyl acetate:hexane=1:9 to 1:1)
  3. customto give a yellow amorphous solid
  4. temperaturewas refluxed for 15 h
  5. temperatureThe whole was refluxed for further 30 min
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by basic silica gel chromatography (ethyl acetate:hexane=1:9 to 1:1, volume ratio)

Sources & evidence

ORD record
ord-58caee0b443f40c9b3897966e6700c09
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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