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

HRID 971142Notes

Reaction equation

HRID 971142 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]([S:19]([CH3:22])(=[O:21])=[O: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)[CH:32]=[CH:31]C=1.[CH3:43][CH2:44]OC(C)=O.CS(C)=[O:51]>[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:31]=[CH:32][C:33]([C:42]5([CH2:41][N:40]6[CH2:39][CH2:38][CH2:37][C:36]6=[O:51])[CH2:44][CH2:43]5)=[CH:34][CH:35]=4)[CH2:16][CH2:17][C:12]=3[C:11]([S:19]([CH3:22])(=[O:20])=[O:21])=[N:10]2)=[CH:7][CH:8]=1

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 13181,10-PhenanthrolineHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 695158511-(4-methoxyphenyl)-3-(methylsulfonyl) 1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one

Product 1

HCID 445814571-(4-Methoxyphenyl)-3-methanesulfonyl-6-{4-[1-(2-oxo-pyrrolidin-1-ylmethyl)cyclopropyl]phenyl}-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-oneYield 25%

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 (0.18 g, 0.56 mmol) and 1-(4-methoxyphenyl)-3-(methylsulfonyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one (0.16 g, 0.47 mmol) were stirred in DMSO (1 mL) under N2. K2CO3 (0.20 g, 1.44 mmol) was added, followed by the addition of CuI (0.030 g, 20 mol %) and 1,10-phenanthroline (0.028 g, 20 mol %). The resulting mixture was heated at 120° C. overnight. 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 flash column chromatography (silica gel, CH2Cl2:EtOAc 1:1, then EtOAc) to give the desired compound (83 mg, yield: 25%). LC/MS (ESI+) 535.2 (M+H)+, tR=3.45 min (10–90% CH3CN/H2O in a 6-min run). 1H NMR (CDCl3) δ 7.45 (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), 3.80 (s, 3H), 3.68 (s, 2H), 3.46 (m, 2H), 3.29 (m, 3H), 3.23 (t, J=6.6 Hz, 2H), 2.25 (m, 2H), 1.86 (m, 2H), 0.86 (m, 4H) ppm.

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 flash column chromatography (silica gel, CH2Cl2:EtOAc 1:1

Sources & evidence

ORD record
ord-09215cba35994b1d9ed96ecc2941675d
Source dataset
uspto-grants-2007_12
Patent number
US07312214B2

Reaction notes

Loading…