Potassium Carbonate → N-(2,5-difluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

HRID 1472614노트

반응식

HRID 1472614 반응식
[F:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([C:16]3[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=3)[CH:11]=2)[C:6]([F:22])=[CH:5][C:3]=1[NH2:4].C([O-])([O-])=O.[K+].[K+].[F:29][C:30]1[CH:35]=[CH:34][C:33]([N:36]2[CH:41]=[CH:40][CH:39]=[C:38]([C:42](Cl)=[O:43])[C:37]2=[O:45])=[CH:32][CH:31]=1>CCOC(C)=O.O.C(Cl)Cl>[F:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([C:16]3[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=3)[CH:11]=2)[C:6]([F:22])=[CH:5][C:3]=1[NH:4][C:42]([C:38]1[C:37](=[O:45])[N:36]([C:33]2[CH:32]=[CH:31][C:30]([F:29])=[CH:35][CH:34]=2)[CH:41]=[CH:40][CH:39]=1)=[O:43]

참가 물질

7

반응물 3

HCID 11430Potassium Carbonate2회HCID 593227742,5-difluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)anilineHCID 596809561-(4-Fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carbonyl chloride2회

생성물 1

HCID 90425853N-(2,5-difluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide수율 180.2%

시약·촉매·용매 3

HCID 962Water용매2회HCID 6344Dichloromethane용매2회HCID 8857Ethyl Acetate용매2회

실험 절차

A mixture of Example A2 (0.324, 1.073 mmol) and K2CO3 (0.178 g, 1.288 mmol) in EtOAc (1.4 mL) and H2O (2.15 mL) was stirred vigorously for 5 min, treated with a solution of Example A3 (0.108 g, 0.429 mmol) in EtOAc (1.4 mL) and stirred at RT for 2 h. The layers were separated, the aqueous layer extracted with DCM and the combined organics were dried over Na2SO4 and concentrated to dryness. The residue was combined with K2CO3 (0.265 g, 1.920 mmol) in DCM (1.4 mL) and H2O (2.1 mL), stirred vigorously for 5 min, treated with a solution of Example A3 (0.403 g, 1.60 mmol) in DCM (1.4 mL) and stirred at RT overnight. The layers were separated, the aqueous layer extracted with DCM and the combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford N-(2,5-difluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (400 mg, 72%) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 12.43 (s, 1H), 8.60 (dd, J=7.3, 2.2 Hz, 1H), 8.55 (dd, J=12.6, 7.2 Hz, 1H), 8.37 (d, J=5.7 Hz, 1H), 8.27 (s, 1H), 8.15 (dd, J=6.6, 2.2 Hz, 1H), 7.97 (s, 1H), 7.62-7.56 (m, 3H), 7.41 (m, 2H), 7.25 (d, J=2.4 Hz, 1H), 6.76-6.71 (m, 2H), 3.84 (s, 3H); MS (ESI) m/z: 518.1 (M+H+).

후처리

  1. customThe layers were separated
  2. extractionthe aqueous layer extracted with DCM
  3. dry with materialthe combined organics were dried over Na2SO4
  4. concentrationconcentrated to dryness
  5. stirringstirred vigorously for 5 min
  6. stirringstirred at RT overnight
  7. customThe layers were separated
  8. extractionthe aqueous layer extracted with DCM
  9. dry with materialthe combined organics were dried over Na2SO4
  10. concentrationconcentrated to dryness
  11. custompurified via silica gel chromatography (MeOH/DCM)

출처 및 근거

ORD 기록
ord-70835506d7db4ccc955f0be652bedd51
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012635B2

반응 노트

불러오는 중…