N,N-Dimethylglycine → 1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-5-[3-(trifluoromethyl)-1H-pyrazol-1-yl]-2,4(1H,3H)-pyrimidinedione

HRID 1925052Notes

Reaction equation

HRID 1925052 reaction equation
I[C:2]1[C:3](=[O:28])[NH:4][C:5](=[O:27])[N:6]([CH2:8][CH2:9][CH2:10][N:11]2[CH2:16][C@H:15]3[C@:13]([C:17]4[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=4)([CH2:14]3)[CH2:12]2)[CH:7]=1.CN(C)CC(O)=O.C([O-])([O-])=O.[K+].[K+].[F:42][C:43]([F:50])([F:49])[C:44]1[CH:48]=[CH:47][NH:46][N:45]=1>CS(C)=O.CCOC(C)=O.[Cu]I>[F:24][C:23]([F:26])([F:25])[C:20]1[CH:21]=[CH:22][C:17]([C@:13]23[CH2:14][C@H:15]2[CH2:16][N:11]([CH2:10][CH2:9][CH2:8][N:6]2[CH:7]=[C:2]([N:46]4[CH:47]=[CH:48][C:44]([C:43]([F:50])([F:49])[F:42])=[N:45]4)[C:3](=[O:28])[NH:4][C:5]2=[O:27])[CH2:12]3)=[CH:18][CH:19]=1

Participants

8

Reactant 4

HCID 673N,N-DimethylglycineHCID 11430Potassium CarbonateHCID 18070343-(Trifluoromethyl)pyrazoleHCID 675197195-iodo-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione

Product 1

HCID 252531381-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-5-[3-(trifluoromethyl)-1H-pyrazol-1-yl]-2,4(1H,3H)-pyrimidinedione

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

5-iodo-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione (Prep10, 60 mg, 0.119 mmol), copper(1+) iodide (24.88 mg, 0.131 mmol), N,N-dimethylglycine (13.47 mg, 0.131 mmol) and K2CO3 (36.1 mg, 0.261 mmol) were dissolved in Dimethyl Sulfoxide (DMSO) (1 ml) to give a light blue suspension with a white solid. 3-(trifluoromethyl)-1H-pyrazole (commercially available from Apollo, 53.3 mg, 0.392 mmol) was added. After shaking at 150° C. for 18 h, the reaction mixture was diluted with EtOAc (5 ml) and the organic phase was washed with water (4×10 ml), then brine (5 ml), dried over Na2SO4, filtered ant the solvent evaporated. The obtained crude was purified by preparative LC-MS. Obtained 12.5 mg of the title compound.

Workup

  1. customto give a light blue suspension with a white solid
  2. washthe organic phase was washed with water (4×10 ml)
  3. dry with materialbrine (5 ml), dried over Na2SO4
  4. filtrationfiltered ant the solvent
  5. customevaporated
  6. customThe obtained crude
  7. customwas purified by preparative LC-MS

Sources & evidence

ORD record
ord-c49addb4a1a4411c84d18807a691f7f1
Source dataset
uspto-grants-2012_05
Patent number
US08178549B2

Reaction notes

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