Tetrahydrofuran → Ethyl{2-[5-{[5-(methylsulfonyl)pyridin-2-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetate

HRID 1042154Notes

Reaction equation

HRID 1042154 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([O:11][C:12]2[CH:13]=[C:14]3[C:18](=[C:19]([O:21][CH:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[CH:20]=2)[NH:17][C:16]([C:28]([NH2:30])=O)=[CH:15]3)=[N:9][CH:10]=1)(=[O:4])=[O:3].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:40])=CC=1.[O:53]1[CH2:57][CH2:56][CH2:55][CH2:54]1.[C:58]([O:61]CC)(=O)[CH3:59]>CCCCCC>[CH2:58]([O:61][C:57](=[O:53])[CH2:56][CH:55]1[S:40][C:28]([C:16]2[NH:17][C:18]3[C:14]([CH:15]=2)=[CH:13][C:12]([O:11][C:8]2[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:10][N:9]=2)=[CH:20][C:19]=3[O:21][CH:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[N:30][CH2:54]1)[CH3:59]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8857Ethyl AcetateHCID 87949Lawesson's reagent4×HCID 66726154HCID 66726154, compound

Product 1

HCID 68090828Ethyl{2-[5-{[5-(methylsulfonyl)pyridin-2-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetateYield 27%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 5-{[5-(methylsulfonyl)pyridin-2-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indole-2-carboxamide (1.41 g), a Lawesson's reagent (1.45 g), and tetrahydrofuran (20 mL) was stirred at 70° C. for 2 hr. To the reaction solution was added a Lawesson's reagent (0.7 g), and the mixture was stirred at 70° C. for 3 hr. Furthermore, a Lawesson's reagent (0.7 g) was added, and the mixture was stirred at 50° C. for 3 days. Furthermore, a Lawesson's reagent (0.7 g) was added, and the mixture was stirred at 70° C. for 2 hr. The reaction solution was concentrated, and the residue was suspended in tetrahydrofuran (10 mL)-toluene (15 mL), tri-n-butylphosphine (1.6 mL) and ethyl 2-butynoate (1.14 mL) were added and the mixture was stirred at 70° C. for 40 min. The reaction solution was diluted with tetrahydrofuran (250 mL), tri-n-butylphosphine (1.6 mL) and ethyl 2-butynoate (1.14 mL) were added, and the mixture was stirred at 70° C. for 2.5 hr. Furthermore, tri-n-butylphosphine (0.8 mL) and ethyl 2-butynoate (1.0 mL) were added, and the mixture was stirred at 70° C. for 2 hr. The reaction solution was concentrated under reduced pressure, and the obtained crude product was subjected to basic silica gel column chromatography (ethyl acetate:hexane=10:90 to 70:30, volume ratio) to give the title compound as a brown amorphous solid (500 mg, yield 27%).

Workup

  1. stirringthe mixture was stirred at 50° C. for 3 days
  2. stirringthe mixture was stirred at 70° C. for 2 hr
  3. concentrationThe reaction solution was concentrated
  4. additionwere added
  5. stirringthe mixture was stirred at 70° C. for 40 min
  6. additionThe reaction solution was diluted with tetrahydrofuran (250 mL), tri-n-butylphosphine (1.6 mL) and ethyl 2-butynoate (1.14 mL)
  7. additionwere added
  8. stirringthe mixture was stirred at 70° C. for 2.5 hr
  9. additionFurthermore, tri-n-butylphosphine (0.8 mL) and ethyl 2-butynoate (1.0 mL) were added
  10. stirringthe mixture was stirred at 70° C. for 2 hr
  11. concentrationThe reaction solution was concentrated under reduced pressure
  12. customthe obtained crude product

Sources & evidence

ORD record
ord-f0353c054f89455188a2bb1ac7964fe2
Source dataset
uspto-grants-2013_10
Patent number
US08557805B2

Reaction notes

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