1,2-Dimethoxyethane → 1-{4-[1-(Difluoromethyl)-1h-pyrazol-4-yl]-2-fluorophenyl}-5-methoxy-3-(1-phenyl-1h-pyrazol-5-yl)pyridazin-4(1h)-one

HRID 1407326

반응식

HRID 1407326 반응식
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH:18]=[C:17]([O:19][CH3:20])[C:16](=[O:21])[C:15]([C:22]3[N:26]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[N:25]=[CH:24][CH:23]=3)=[N:14]2)=[C:9]([F:33])[CH:8]=1)(=O)=O.[F:36][CH:37]([F:52])[N:38]1[CH:42]=[C:41](B2OC(C)(C)C(C)(C)O2)[CH:40]=[N:39]1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:36][CH:37]([F:52])[N:38]1[CH:42]=[C:41]([C:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH:18]=[C:17]([O:19][CH3:20])[C:16](=[O:21])[C:15]([C:22]4[N:26]([C:27]5[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=5)[N:25]=[CH:24][CH:23]=4)=[N:14]3)=[C:9]([F:33])[CH:8]=2)[CH:40]=[N:39]1

참가 물질

7

반응물 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 497579861-(difluoromethyl)-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 580722213-fluoro-4-[5-methoxy-4-oxo-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-1(4H)-yl]phenyl trifluoromethanesulfonate

생성물 1

HCID 580722191-{4-[1-(Difluoromethyl)-1h-pyrazol-4-yl]-2-fluorophenyl}-5-methoxy-3-(1-phenyl-1h-pyrazol-5-yl)pyridazin-4(1h)-one수율 85%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매2회

실험 절차

A mixture of 3-fluoro-4-[5-methoxy-4-oxo-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-1(4H)-yl]phenyl trifluoromethanesulfonate (230 mg, 0.45 mmol), 1-(difluoromethyl)-1H-pyrazole-4-boronic acid pinacol ester (122 mg, 0.50 mmol), Pd(PPh3)4 (17 mg, 0.015 mmol), Na2CO3 (106 mg, 1.0 mmol), DME (4 mL), and H2O (1 mL) was refluxed for 3 h under Ar atmosphere. After cooling to room temperature, the reaction mixture was poured into water and extracted with AcOEt. The extract was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography eluting with AcOEt and recrystallized from MeOH/H2O to give the title compound (183 mg, 85% yield) as a white solid: mp 185-187° C.; 1H NMR (300 MHz, CDCl3): δ ppm 3.92 (3H, s), 6.41 (1H, t, J=8.3 Hz), 7.03-7.48 (10H, m), 7.79 (1H, d, J=1.9 Hz), 7.83 (1H, d, J=2.3 Hz), 7.91 (1H, d, J=0.8 Hz). LC-MS (ESI) m/z 479 [M+H]+. Anal. Calcd for C24H17F3N6O2: C, 60.25; H, 3.58; N, 17.57. Found: C, 60.19; H, 3.48; N, 17.52.

후처리

  1. temperaturewas refluxed for 3 h under Ar atmosphere
  2. extractionextracted with AcOEt
  3. washThe extract was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by basic silica gel column chromatography
  7. washeluting with AcOEt
  8. customrecrystallized from MeOH/H2O

출처 및 근거

ORD 기록
ord-738f171433fb457ca49bb69f7e046d1e
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08916566B2

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