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 971147Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 971147
[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

Komponenten

7

Edukt 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

Produkt 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-oneAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 1

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

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-166f51f106c94635ad924b1c0a5ee498
Quelldatensatz
uspto-grants-2007_12
Patentnummer
US07312214B2

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