Diisopropylethylamine → 5-(6-methyl-2-pyridinyl)-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2,4(1H,3H)-pyrimidinedione dihydrochloride

HRID 12780Notes

Reaction equation

HRID 12780 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[N:13]=2)[C:9](=[O:19])[NH:8][C:7]1=[O:20].[F:21][C:22]([F:36])([F:35])[C:23]1[CH:28]=[CH:27][C:26]([C@:29]23[CH2:34][C@H:33]2[CH2:32][NH:31][CH2:30]3)=[CH:25][CH:24]=1.CCN(C(C)C)C(C)C>CCO>[ClH:1].[ClH:1].[CH3:18][C:14]1[N:13]=[C:12]([C:10]2[C:9](=[O:19])[NH:8][C:7](=[O:20])[N:6]([CH2:5][CH2:4][CH2:3][CH2:2][N:31]3[CH2:32][C@H:33]4[C@:29]([C:26]5[CH:25]=[CH:24][C:23]([C:22]([F:21])([F:36])[F:35])=[CH:28][CH:27]=5)([CH2:34]4)[CH2:30]3)[CH:11]=2)[CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 589942001-(4-Chloro-butyl)-5-(6-methyl-pyridin-2-yl)-1H-pyrimidine-2,4-dioneHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Product 1

HCID 686915305-(6-methyl-2-pyridinyl)-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2,4(1H,3H)-pyrimidinedione dihydrochloride

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 1-(4-chloro-butyl)-5-(6-methyl-pyridin-2-yl)-1H-pyrimidine-2,4-dione (Prep51, 95 mg, 0.32 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 74 mg, 0.32 mmol), and TEA (98 μl, 1 mmol) in absolute EtOH (4 mL) was refluxed for 48 h. Then dry DIPEA (83.6 mg, 0.64 mmol) was added and the mixture placed in a microwave oven and irradiated at 125° C. for 4 hours. The solvent was removed under vacuum and the residue was partitioned between water and ethyl acetate. The organic phase was dried (Na2SO4), filtered and evaporated. The residue was dissolved in DCM and treated with PS-isocyanate resin (250 mg) under stirring for 2 h. After filtration and evaporation of the solvent, the crude was purified by flash chromatography with DCM-MeOH—NH4OH (98-2-0.2) to give the title compound as free base.

Workup

  1. customthe mixture placed in a microwave oven
  2. customirradiated at 125° C. for 4 hours
  3. customThe solvent was removed under vacuum
  4. customthe residue was partitioned between water and ethyl acetate
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionThe residue was dissolved in DCM
  9. additiontreated with PS-isocyanate resin (250 mg)
  10. filtrationAfter filtration and evaporation of the solvent
  11. customthe crude was purified by flash chromatography with DCM-MeOH—NH4OH (98-2-0.2)

Sources & evidence

ORD record
ord-c1f25d7c76c845f38c8ea757d242b0f0
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Reaction notes

Loading…