Tetrahydro-2-(2-propynyloxy)-2H-pyran → HCID 21904872, compound

HRID 1247413Notes

Reaction equation

HRID 1247413 reaction equation
[C:1]([C:3]1[CH:30]=[CH:29][C:6]([CH2:7][NH:8][C:9]([CH:11]([O:27][CH3:28])[C:12]2[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=2OS(C(F)(F)F)(=O)=O)=[O:10])=[CH:5][CH:4]=1)#[N:2].[CH2:31]([O:34][CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][O:36]1)[C:32]#[CH:33]>CN(C=O)C>[C:1]([C:3]1[CH:30]=[CH:29][C:6]([CH2:7][NH:8][C:9](=[O:10])[CH:11]([C:12]2[C:13]([C:33]#[C:32][CH2:31][O:34][CH:35]3[CH2:40][CH2:39][CH2:38][CH2:37][O:36]3)=[CH:14][CH:15]=[CH:16][C:17]=2[F:18])[O:27][CH3:28])=[CH:5][CH:4]=1)#[N:2]

Participants

4

Reactant 2

HCID 98609Tetrahydro-2-(2-propynyloxy)-2H-pyranHCID 86593053HCID 86593053, compound

Product 1

HCID 21904872HCID 21904872, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of (RS)-trifluoro-methanesulfonic acid 2-[(4-cyano-benzylcarbamoyl)-methoxy-methyl]-3-fluoro-phenyl ester (520 mg, example 279.1) in DMF (10 ml) was heated to 100° C. and treated with TEA (0.49 ml), tetrahydro-2-(2-propynyloxy)-2H-pyrane (0.33 ml) and Cu(I)I (18 mg). The reaction mixture was degassed by passing a stream of Argon through the reaction mixture. Then bis(triphenylphosphine)palladium(II)chloride (32 mg) was added. The reaction was heated for 6 hrs at 100° C. After cooling to rt, the mixture was concentrated. The residue was taken up in EtOAc and H2O. After filtration through a glass microfibre filter, phases were separated. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The crude product was purified by flash chromatography (cyclohexane=>cyclohexane/EtOAc 3:2) to give (RS)-N-(4-cyano-benzyl)-2-{2-fluoro-6-[3-(tetrahydro-pyran-2-yloxy)-prop-1-ynyl]-phenyl}-2-methoxy-acetamide as off-white solid. MS 454.3 ([M+NH4]+)

Workup

  1. customThe reaction mixture was degassed
  2. additionThen bis(triphenylphosphine)palladium(II)chloride (32 mg) was added
  3. temperatureThe reaction was heated for 6 hrs at 100° C
  4. temperatureAfter cooling to rt
  5. concentrationthe mixture was concentrated
  6. filtrationAfter filtration through a glass microfibre
  7. filtrationfilter
  8. customphases were separated
  9. washThe organic layer was washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude product was purified by flash chromatography (cyclohexane=>cyclohexane/EtOAc 3:2)

Sources & evidence

ORD record
ord-6acae6845b9f4304ab45ad40ba078d67
Source dataset
uspto-grants-2006_10
Patent number
US07129238B2

Reaction notes

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