Hydrochloric Acid → 1-{4-[1-(4-methoxyphenyl)-7-oxo-3-(trifluoromethyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl]phenyl}cyclobutane carboxylic acid

HRID 971135Notes

Reaction equation

HRID 971135 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]3[C:14](=[O:18])[NH:15][CH2:16][CH2:17][C:12]=3[C:11]([C:19]([F:22])([F:21])[F:20])=[N:10]2)=[CH:5][CH:4]=1.[C:23]([O-:26])([O-])=[O:24].[K+].[K+].N1[C:42]2[C:33](=[CH:34][CH:35]=[C:36]3[C:41]=2N=[CH:39][CH:38]=[CH:37]3)C=CC=1.Cl.[CH3:44]S(C)=O>[Cu]I.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:13]3[C:14](=[O:18])[N:15]([C:33]4[CH:34]=[CH:35][C:36]([C:37]5([C:23]([OH:26])=[O:24])[CH2:38][CH2:39][CH2:44]5)=[CH:41][CH:42]=4)[CH2:16][CH2:17][C:12]=3[C:11]([C:19]([F:22])([F:20])[F:21])=[N:10]2)=[CH:7][CH:8]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 679Dimethyl SulfoxideHCID 13181,10-PhenanthrolineHCID 11430Potassium CarbonateHCID 218914731-(4-Methoxy-phenyl)-3-trifluoromethyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one

Product 1

HCID 695157611-{4-[1-(4-methoxyphenyl)-7-oxo-3-(trifluoromethyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl]phenyl}cyclobutane carboxylic acidYield 97%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
130 °C

Procedure

Part C. The product from part B (1.20 g, 3.97 mmol) and 1-(4-methoxyphenyl)-3-(trifluoromethyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one (0.87 g, 2.8 mmol) were stirred in DMSO (3 mL) under N2. K2CO3 (1.16 g, mmol, 3.0 eq) was added followed by the addition of 1,10-phenanthroline (100 mg, 20 mol %) and CuI (106 mg, 20 mol %). The resulting mixture was stirred at 130° C. overnight. LC-MS showed completion of the reaction. EtOAc was added to the cooled solution. The solution was acidified with 1N HCl, and the organic layer was washed with H2O and and brine, dried over MgSO4, filtered, and concentrated to afford 1-{4-[1-(4-methoxyphenyl)-7-oxo-3-(trifluoromethyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl]phenyl}cyclobutane carboxylic acid (1.34 g, yield 97%). LC/MS (ESI+) 486.6 (M+H)+, tR=2.81 min (10–90% CH3CN/H2O in a 4-min run).

Workup

  1. customcompletion of the reaction
  2. washthe organic layer was washed with H2O and and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7c8d284e0252441194b3e3af414f671f
Source dataset
uspto-grants-2007_12
Patent number
US07312214B2

Reaction notes

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