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 971147노트

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HRID 971147 반응식
[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

참가 물질

7

반응물 5

HCID 679Dimethyl SulfoxideHCID 13181,10-PhenanthrolineHCID 8857Ethyl Acetate2회HCID 11430Potassium CarbonateHCID 218914731-(4-Methoxy-phenyl)-3-trifluoromethyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one

생성물 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-one수율 45%

시약·촉매·용매 1

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

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온도
120 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-166f51f106c94635ad924b1c0a5ee498
출처 데이터셋
uspto-grants-2007_12
특허 번호
US07312214B2

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