Potassium Carbonate → 5-(3-methyl-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 1925060Notes

Reaction equation

HRID 1925060 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+].[CH3:55][C:56]1[CH:60]=[CH:59][NH:58][N:57]=1.[N-]=C=O>C1(C)C=CC=CC=1.C(Cl)Cl.[Cu](I)I>[CH3:55][C:56]1[CH:60]=[CH:59][N:58]([C:22]2[C:23](=[O:48])[NH:24][C:25](=[O:47])[N:26]([CH2:28][CH2:29][CH2:30][N:31]3[CH2:36][C@H:35]4[C@:33]([C:37]5[CH:42]=[CH:41][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:39][CH:38]=5)([CH2:34]4)[CH2:32]3)[CH:27]=2)[N:57]=1

Participants

9

Reactant 5

HCID 11430Potassium CarbonateHCID 105034IsocyanateHCID 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 178428694HCID 178428694, compound

Product 1

HCID 252532915-(3-methyl-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

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

Copper iodide (56.5 mg, 0.297 mmol), (1R,2R)—N,N′-dimethyl-1,2-cyclohexanediamine methyl[(1R,2R)-2-(methylamino)cyclohexyl]amine (169 mg, 1.187 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, 150 mg, 0.297 mmol) and K2CO3 (86 mg, 0.623 mmol) were dissolved in Toluene (1.5 ml) to give a blue suspension with a white precipitate. 3-methyl-1H-pyrazole (commercially available from ABCR, 0.029 ml, 0.356 mmol) was added thereto. After shaking at 110° C. for 18 h, the reaction mixture was filtered and the solvent evaporated. The obtained crude was dissolved in 20 mL of DCM and 500 mg of PS-thiol resin and 2.0 g of MP-isocyanate resin were added to blue solution. The obtained suspension was shaken for 2 h at 35° C., then filtered and the solvent evaporated. The resulting mixture was iteratively purified (two times) by preparative LC-MS. Obtained 51.8 mg of the title compound.

Workup

  1. customto give a blue suspension with a white precipitate
  2. filtrationthe reaction mixture was filtered
  3. customthe solvent evaporated
  4. customThe obtained crude
  5. stirringThe obtained suspension was shaken for 2 h at 35° C.
  6. filtrationfiltered
  7. customthe solvent evaporated
  8. customThe resulting mixture was iteratively purified (two times) by preparative LC-MS

Sources & evidence

ORD record
ord-b11cc020cbca4882be1514e00a61f62a
Source dataset
uspto-grants-2012_05
Patent number
US08178549B2

Reaction notes

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