Potassium Carbonate → 1-[2,4-dioxo-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]-1H-pyrazole-3-carbonitrile

HRID 1925062Notes

Reaction equation

HRID 1925062 reaction equation
CN[C@@H]1CCCC[C@H]1NC.CN[C@@H]1CCCC[C@H]1NC.I[C:22]1[C:23](=[O:48])[NH:24][C:25](=[O:47])[N:26]([CH2:28][CH2:29][CH2:30][N:31]2[CH2:36][C@H:35]3[C@:33]([C:37]4[CH:42]=[CH:41][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:39][CH:38]=4)([CH2:34]3)[CH2:32]2)[CH:27]=1.C([O-])([O-])=O.[K+].[K+].[NH:55]1[CH:59]=[CH:58][C:57]([C:60]#[N:61])=[N:56]1>C1(C)C=CC=CC=1.[Cu]I>[O:47]=[C:25]1[NH:24][C:23](=[O:48])[C:22]([N:55]2[CH:59]=[CH:58][C:57]([C:60]#[N:61])=[N:56]2)=[CH:27][N:26]1[CH2:28][CH2:29][CH2:30][N:31]1[CH2:36][C@H:35]2[C@:33]([C:37]3[CH:42]=[CH:41][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:39][CH:38]=3)([CH2:34]2)[CH2:32]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 67519718(1R,2R)-N,N'-dimethyl-1,2-cyclohexanediamine methyl[(1R,2R)-2-(methylamino)cyclohexyl]amineHCID 675197195-iodo-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedioneHCID 178510229HCID 178510229, compound

Product 1

HCID 252532921-[2,4-dioxo-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]-1H-pyrazole-3-carbonitrile

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

Copper(1+) iodide (50.1 mg, 0.263 mmol), (1R,2R)—N,N′-dimethyl-1,2-cyclohexanediamine methyl[(1R,2R)-2-(methylamino)cyclohexyl]amine (0.166 ml, 1.053 mmol), 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, 133 mg, 0.263 mmol) and K2CO3 (76 mg, 0.553 mmol) were dissolved in Toluene (1 ml) to give a blue suspension with a white precipitate. 1H-pyrazole-3-carbonitrile (commercially available from Tyger, 29.4 mg, 0.316 mmol) was added thereto. After shaking at 110° C. for 18 h, the reaction mixture was filtered and the solvent evaporated. The obtained residue was purified by flash chromatography (eluent: pure EtOAc for 4CV, then from pure EtOAc to EtOAc/MeOH 9:1 in 10 CV, then EtOAc/MeOH 9:1 for 10 CV; 12M column) to obtain 14.5 mg of our target compound that was further purified on a SCX cartridge and eluted with a 2M solution of ammonia in MeOH. The resulting solution was evaporated in vacuo to obtained 10.9 mg of title compound as a white solid.

Workup

  1. customto give a blue suspension with a white precipitate
  2. filtrationthe reaction mixture was filtered
  3. customthe solvent evaporated
  4. customThe obtained residue was purified by flash chromatography (eluent
  5. custom12M column) to obtain 14.5 mg of our target compound that
  6. customwas further purified on a SCX cartridge
  7. washeluted with a 2M solution of ammonia in MeOH
  8. customThe resulting solution was evaporated in vacuo

Sources & evidence

ORD record
ord-16c7c7ce16c144cf88efe11eee9fe02b
Source dataset
uspto-grants-2012_05
Patent number
US08178549B2

Reaction notes

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