Ethyl 2-butynoate → Ethyl (2-{5-[4-(methylsulfonyl)phenoxy]-7-(tetrahydro-2H-pyran-4-ylmethoxy)-1H-indol-2-yl}-4,5-dihydro-1,3-thiazol-5-yl)acetate

HRID 1188983Notes

Reaction equation

HRID 1188983 reaction equation
[CH3:1][S:2]([C:5]1[CH:31]=[CH:30][C:8]([O:9][C:10]2[CH:11]=[C:12]3[C:16](=[C:17]([O:19][CH2:20][CH:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[CH:18]=2)[NH:15][C:14]([C:27]([NH2:29])=O)=[CH:13]3)=[CH:7][CH:6]=1)(=[O:4])=[O:3].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:41])=CC=1.[C:54]([O:59][CH2:60][CH3:61])(=[O:58])[C:55]#[C:56][CH3:57]>O1CCCC1.C1(C)C=CC=CC=1.C(P(CCCC)CCCC)CCC>[CH3:1][S:2]([C:5]1[CH:31]=[CH:30][C:8]([O:9][C:10]2[CH:11]=[C:12]3[C:16](=[C:17]([O:19][CH2:20][CH:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[CH:18]=2)[NH:15][C:14]([C:27]2[S:41][CH:56]([CH2:55][C:54]([O:59][CH2:60][CH3:61])=[O:58])[CH2:57][N:29]=2)=[CH:13]3)=[CH:7][CH:6]=1)(=[O:4])=[O:3]

Participants

7

Reactant 3

HCID 78043Ethyl 2-butynoateHCID 87949Lawesson's reagentHCID 668985525-[4-(Methylsulfonyl)phenoxy]-7-(tetrahydro-2H-pyran-4-ylmethoxy)-1H-indole-2-carboxamide

Product 1

HCID 68381675Ethyl (2-{5-[4-(methylsulfonyl)phenoxy]-7-(tetrahydro-2H-pyran-4-ylmethoxy)-1H-indol-2-yl}-4,5-dihydro-1,3-thiazol-5-yl)acetateYield 48%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×HCID 13831TributylphosphineSolvent

Conditions

Temperature
50 °C

Procedure

5-[4-(Methylsulfonyl)phenoxy]-7-(tetrahydro-2H-pyran-4-ylmethoxy)-1H-indole-2-carboxamide (500 mg) was dissolved in tetrahydrofuran (20 mL), Lawesson's reagent (455 mg) was added, and the mixture was stirred at 50° C. for 1 hr. The reaction solution was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography (ethyl acetate:hexane=20:80 to 70:30, volume ratio) to give a yellow oil. The obtained yellow oil was dissolved in a mixed solvent of tetrahydrofuran (10 mL)-toluene (15 mL), ethyl 2-butynoate (0.26 mL) and tributylphosphine (0.30 mL) were added, and the mixture was stirred at 50° C. for 2.5 hr. The reaction solution was concentrated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (ethyl acetate:hexane=10:90 to 100:0, volume ratio) to give the title compound (310 mg, yield 48%) as an orange oil. MS 573 (MH+).

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. customto give a yellow oil
  3. additionwere added
  4. stirringthe mixture was stirred at 50° C. for 2.5 hr
  5. concentrationThe reaction solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-15f0df746ce9425680ee5c0d4b56b74c
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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