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

HRID 1925051Notes

Reaction equation

HRID 1925051 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.[NH:29]1[CH:33]=[CH:32][CH:31]=[N:30]1.CN(C)CC(O)=O.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.CCOC(C)=O.[Cu](I)I>[N:29]1([C:2]2[C:3](=[O:28])[NH:4][C:5](=[O:27])[N:6]([CH2:8][CH2:9][CH2:10][N:11]3[CH2:16][C@H:15]4[C@:13]([C:17]5[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=5)([CH2:14]4)[CH2:12]3)[CH:7]=2)[CH:33]=[CH:32][CH:31]=[N:30]1

Participants

8

Reactant 4

HCID 673N,N-DimethylglycineHCID 1048PyrazoleHCID 11430Potassium CarbonateHCID 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 252531375-(1H-pyrazol-1-yl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedioneYield 18.5%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 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), 1H-pyrazole (26.7 mg, 0.392 mmol), copper 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 colorless suspension with a white solid. 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 residue was purified by preparative LC-MS to give 9.8 mg (18.48% yield) of the title compound as a yellow oil.

Workup

  1. customto give a colorless 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 residue was purified by preparative LC-MS

Sources & evidence

ORD record
ord-9f5699f762f846f49f921ce3a91d2358
Source dataset
uspto-grants-2012_05
Patent number
US08178549B2

Reaction notes

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