Water → 2-[(4,4-difluorocyclohexyl)oxy]-3-[4-(2,2,2-trifluoroethoxy)phenyl]pyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

HRID 570698Notes

Reaction equation

HRID 570698 reaction equation
[H-].[Na+].[F:3][C:4]1([F:11])[CH2:9][CH2:8][CH:7]([OH:10])[CH2:6][CH2:5]1.C(S[C:16]1[N:17]([C:28]2[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]([F:39])([F:38])[F:37])=[CH:30][CH:29]=2)[C:18](=[O:27])[C:19]2[CH:25]=[CH:24][C:23](=[O:26])[NH:22][C:20]=2[N:21]=1)CC.O>O1CCCC1>[F:3][C:4]1([F:11])[CH2:9][CH2:8][CH:7]([O:10][C:16]2[N:17]([C:28]3[CH:29]=[CH:30][C:31]([O:34][CH2:35][C:36]([F:39])([F:38])[F:37])=[CH:32][CH:33]=3)[C:18](=[O:27])[C:19]3[CH:25]=[CH:24][C:23](=[O:26])[NH:22][C:20]=3[N:21]=2)[CH2:6][CH2:5]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 5463004,4-Difluorocyclohexan-1-olHCID 86685358HCID 86685358, compound

Product 1

HCID 866853612-[(4,4-difluorocyclohexyl)oxy]-3-[4-(2,2,2-trifluoroethoxy)phenyl]pyrido[2,3-d]pyrimidine-4,7(3H,8H)-dioneYield 39.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of sodium hydride (60% in oil, 19 mg) in tetrahydrofuran (5 ml) was added 4,4-difluorocyclohexanol (109 mg) at room temperature, and the mixture was stirred at room temperature for 10 min. To the reaction mixture was added 2-(propylsulfanyl)-3-[4-(2,2,2-trifluoroethoxy)phenyl]pyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (165 mg), and the mixture was stirred at room temperature for 5 hr. The reaction mixture was added to water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), and recrystallized from a mixed solvent of hexane/ethyl acetate to give the title compound (75 mg).

Workup

  1. stirringthe mixture was stirred at room temperature for 5 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  7. customrecrystallized from a mixed solvent of hexane/ethyl acetate

Sources & evidence

ORD record
ord-c4fae2e23e474d01a37369442636685e
Source dataset
uspto-grants-2015_05
Patent number
US09023858B2

Reaction notes

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