Hydrochloric Acid → HCID 59463592, compound

HRID 1713107Notes

Reaction equation

HRID 1713107 reaction equation
C(OC([N:8]1[CH2:31][CH2:30][C:11]2[N:12]=[C:13]([C:16]3[CH:21]=[CH:20][C:19](OS(C(F)(F)F)(=O)=O)=[CH:18][CH:17]=3)[N:14]=[CH:15][C:10]=2[CH2:9]1)=O)(C)(C)C.[CH2:32]([O:36]C=C)[CH2:33]CC.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC=C)=C.Cl.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[N:12]1[C:11]2[CH2:30][CH2:31][NH:8][CH2:9][C:10]=2[CH:15]=[N:14][C:13]=1[C:16]1[CH:17]=[CH:18][C:19]([C:32](=[O:36])[CH3:33])=[CH:20][CH:21]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 8024Vinyl etherHCID 8108Butyl vinyl etherHCID 10340Sodium CarbonateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 58984591HCID 58984591, compound

Product 1

HCID 59463592HCID 59463592, compound

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 2-(4-trifluoromethanesulfonyloxy-phenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester (918 mg, 2.0 mmol) in dry DMF (10 ml) is added n-butylvinyl ether (1.02 g, 10 mmol, 5.0 eq.), TEA (404 mg, 4.0 mmol, 2.0 eq.), 1,3-bis(diphenylphosphino)propane (29 mg, 0.055 mmol, 0.0276 eq.) and palladium acetate (11.3 mg, 0.05 mmol, 0.025 eq.) under nitrogen. The resulting mixture is stirred at 80° C. for 7 hr. Water (30 ml) is added to quench the reaction, and the mixture is extracted with EtOAc (30 ml×3). The combined organic phase is washed with water and brine, dried over sodium sulfate, and concentrated. The crude product is purified by silica gel flash chromatography (hexane/EtOAc 5:1) to give a mixture of the vinyl ether and the ketone product, which is dissolved in EtOAc (30 ml), and then treated with concentrated hydrochloric acid (3.0 ml). The mixture is stirred at rt for 2 hr, and then basified with saturated sodium carbonate solution. The organic phase is collected, and the aqueous phase is extracted with DCM twice. The combined organic phase is dried over sodium sulfate, and concentrated to give the title compound. MS (+VE) m/z 254.1 (M++1).

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture is extracted with EtOAc (30 ml×3)
  4. washThe combined organic phase is washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe crude product is purified by silica gel flash chromatography (hexane/EtOAc 5:1)
  8. customto give
  9. stirringThe mixture is stirred at rt for 2 hr
  10. customThe organic phase is collected
  11. extractionthe aqueous phase is extracted with DCM twice
  12. dry with materialThe combined organic phase is dried over sodium sulfate
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-0d6619bfc2144352bab0c8f51f6e9a2f
Source dataset
uspto-grants-2010_09
Patent number
US07795262B2

Reaction notes

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