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

HRID 468784ノート

反応式

HRID 468784 の反応式
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

参加物

8

反応物 5

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 80376Cyclopropanecarboxamide2 回HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)2 回HCID 866749456-Chloro-2-(5-fluoro-2-methylphenyl)-4-methyl-1,7-naphthyridine

生成物 1

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

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-108ef2af99d34ee3a7e623c0686b0b38
出典データセット
uspto-grants-2014_01
特許番号
US08623889B2

反応ノート

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