Potassium Carbonate → 5-methyl-4-(3-pyridinyl)-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2(1H)-pyrimidinone hydrochloride

HRID 1514445Notes

Reaction equation

HRID 1514445 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[CH:11]=[C:10]([CH3:12])[C:9]([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)=[N:8][C:7]1=[O:19].[F:20][C:21]([F:35])([F:34])[C:22]1[CH:27]=[CH:26][C:25]([C@:28]23[CH2:33][C@H:32]2[CH2:31][NH:30][CH2:29]3)=[CH:24][CH:23]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[ClH:1].[CH3:12][C:10]1[C:9]([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)=[N:8][C:7](=[O:19])[N:6]([CH2:5][CH2:4][CH2:3][CH2:2][N:30]2[CH2:31][C@H:32]3[C@:28]([C:25]4[CH:24]=[CH:23][C:22]([C:21]([F:20])([F:35])[F:34])=[CH:27][CH:26]=4)([CH2:33]3)[CH2:29]2)[CH:11]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 592427851-(4-Chloro-butyl)-5-methyl-4-pyridin-3-yl-1H-pyrimidin-2-oneHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Product 1

HCID 687019445-methyl-4-(3-pyridinyl)-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2(1H)-pyrimidinone hydrochlorideYield 12%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 1-(4-chloro-butyl)-5-methyl-4-pyridin-3-yl-1H-pyrimidin-2-one (Prep12, 86 mg, 0.31 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 63 mg, 0.28 mmol), KI (2 mg) and K2CO3 (43 mg, 0.31 mmol) in DMF (2 ml) was placed in a microwave oven and irradiated at 115° C. for 1 hour. After cooling, the solution was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried (Na2SO4) and evaporated The solvent was removed under vacuum and the residue was redissolved in DCM and filtered, the filtrate was stirred in the presence of PS-isocyanate (350 mg) for 3 hours. The mixture was filtered and the solvent removed under vacuum. The crude was purified by flash chromatography with DCM-MeOH—NH4OH (99-1-0.1) to give the title compound (17 mg, 4% yield) as a free base.

Workup

  1. customirradiated at 115° C. for 1 hour
  2. temperatureAfter cooling
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. customevaporated The solvent
  7. customwas removed under vacuum
  8. dissolutionthe residue was redissolved in DCM
  9. filtrationfiltered
  10. filtrationThe mixture was filtered
  11. customthe solvent removed under vacuum
  12. customThe crude was purified by flash chromatography with DCM-MeOH—NH4OH (99-1-0.1)

Sources & evidence

ORD record
ord-b12f4a8abae5457ea46f773074605b4c
Source dataset
uspto-grants-2012_07
Patent number
US08222266B2

Reaction notes

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