Dimethyl Sulfoxide → 1-(4-Methoxyphenyl)-6-{4-[1-(2-oxo-pyrrolidin-1-yl)-cyclopropyl]phenyl}-3-trifluoromethyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one

HRID 971147Notes

Reaction equation

HRID 971147 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]3[C:14](=O)[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.[K+].[K+].N1[C:42]2[C:33](=[CH:34][CH:35]=[C:36]3[C:41]=2[N:40]=[CH:39][CH:38]=[CH:37]3)C=CC=1.CCO[C:46]([CH3:48])=[O:47].[CH3:49]S(C)=O>[Cu]I>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:13]3[C:23](=[O:26])[N:15]([C:14]4[CH:34]=[CH:35][C:36]([C:41]5([N:40]6[CH2:39][CH2:38][CH2:48][C:46]6=[O:47])[CH2:42][CH2:33]5)=[CH:37][CH:49]=4)[CH2:16][CH2:17][C:12]=3[C:11]([C:19]([F:20])([F:22])[F:21])=[N:10]2)=[CH:7][CH:8]=1

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 13181,10-PhenanthrolineHCID 8857Ethyl Acetate2×HCID 11430Potassium CarbonateHCID 218914731-(4-Methoxy-phenyl)-3-trifluoromethyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one

Product 1

HCID 445815911-(4-Methoxyphenyl)-6-{4-[1-(2-oxo-pyrrolidin-1-yl)-cyclopropyl]phenyl}-3-trifluoromethyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-oneYield 45%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
120 °C

Procedure

Part C. The product from Part B (64 mg, 0.196 mmol) and 1-(4-methoxyphenyl)-3-(trifluoromethyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one (0.061 g, 0.196 mmol) were stirred in DMSO (0.3 mL) under N2. K2CO3 (0.067 g, 0.49 mmol, 2.5 eq) was added, followed by the addition of CuI (0.037 g, 0.194 mmol) and 1,10-phenanthroline (0.020 g, 0.108 mmol). The resulting mixture was heated at 120° C. for 3 h. After cooling, it was extracted with EtOAc (2×), washed with H2O and brine, dried over MgSO4, filtered, and concentrated to dryness. The residue was purified by FCC (silica gel, CH2Cl2:EtOAc=1:1, then EtOAc) to give 1-(4-methoxyphenyl)-6-{4-[1-(2-oxo-pyrrolidin-1-yl)-cyclopropyl]phenyl}-3-trifluoromethyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one (45 mg, yield: 45%). 1H NMR (CDCl3) δ 7.46 (d, J=8.8 Hz, 2H), 7.25 (AA′BB′, J=8.6 Hz, 4H), 6.91 (d, J=9.2 Hz, 2H), 4.10 (t, J=6.6 Hz, 2H), 3.81 (s, 3H), 3.38 (t, J=7.2 Hz, 2H), 3.14 (t, J=6.6 Hz, 2H), 2.37 (t, J=7.7 Hz, 2H), 1.98 (q, J=7.7 Hz, 2H), 1.32 (m, 2H), 1.21 (m, 2H) ppm. HRMS C27H26F3N3O4 (M+H)+ 511.1931 calcd for 511.1958.

Workup

  1. temperatureAfter cooling
  2. extractionit was extracted with EtOAc (2×)
  3. washwashed with H2O and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe residue was purified by FCC (silica gel, CH2Cl2

Sources & evidence

ORD record
ord-166f51f106c94635ad924b1c0a5ee498
Source dataset
uspto-grants-2007_12
Patent number
US07312214B2

Reaction notes

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