Cesium carbonate → N-(2-(5-fluoro-2-methylphenyl)-4-methyl-1,7-naphthyridin-6-yl)cyclopropanecarboxamide

HRID 468784노트

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HRID 468784 반응식
Cl[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[CH3:19])[CH:6]=[C:5]2[CH3:20].[CH:21]1([C:24]([NH2:26])=[O:25])[CH2:23][CH2:22]1.O1CCOCC1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:18][C:16]1[CH:15]=[CH:14][C:13]([CH3:19])=[C:12]([C:7]2[CH:6]=[C:5]([CH3:20])[C:4]3[C:9](=[CH:10][N:11]=[C:2]([NH:26][C:24]([CH:21]4[CH2:23][CH2:22]4)=[O:25])[CH:3]=3)[N:8]=2)[CH:17]=1

참가 물질

8

반응물 5

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 80376Cyclopropanecarboxamide2회HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)2회HCID 866749456-Chloro-2-(5-fluoro-2-methylphenyl)-4-methyl-1,7-naphthyridine

생성물 1

HCID 67976405N-(2-(5-fluoro-2-methylphenyl)-4-methyl-1,7-naphthyridin-6-yl)cyclopropanecarboxamide수율 78%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매2회HCID 8857Ethyl Acetate용매

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온도
90 °C

실험 절차

To a mixture of 6-chloro-2-(5-fluoro-2-methylphenyl)-4-methyl-1,7-naphthyridine (140.1 mg, 0.4886 mmol) and cyclopropanecarboxamide (85.9 mg, 1.01 mmol) in 1,4-dioxane (4.0 mL, 51 mmol) was added palladium (II) acetate (11.9 mg, 0.053 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (38.8 mg, 0.067 mmol), and cesium carbonate (417.3 mg, 1.281 mmol). The reaction vial was purged with nitrogen gas and then heated at 90° C. under a nitrogen balloon for 5 hours. Cyclopropanecarboxamide (38.0 mg, 0.447 mmol), palladium (II) acetate (32.0 mg, 0.143 mmol), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (78.9 mg, 0.136 mmol) were added and the reaction heated at 100° C. for 15 hours. The reaction mixture was then diluted in ethyl acetate, washed with water and brine, dried over MgSO4, and evaporated in vacuo. The crude product was purified via reverse phase HPLC and lyophilized to yield 0.1227 g (78%) of N-(2-(5-fluoro-2-methylphenyl)-4-methyl-1,7-naphthyridin-6-yl)cyclopropanecarboxamide. LCMS (ESI): RT (min)=5.239, M+H=336.1, method=E; 1H NMR (400 MHz, DMSO) δ 11.12 (s, 1H), 9.21 (s, 1H), 8.65 (s, 1H), 7.79 (s, 1H), 7.38 (m, 3.6H), 7.23 (td, J=8.5, 2.8 Hz, 1H), 2.66 (s, 3H), 2.37 (s, 3H), 2.11 (s, 1H), 0.93-0.81 (m, 4H).

후처리

  1. customThe reaction
  2. customvial was purged with nitrogen gas
  3. temperaturethe reaction heated at 100° C. for 15 hours
  4. washwashed with water and brine
  5. dry with materialdried over MgSO4
  6. customevaporated in vacuo
  7. customThe crude product was purified via reverse phase HPLC

출처 및 근거

ORD 기록
ord-108ef2af99d34ee3a7e623c0686b0b38
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08623889B2

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