5-chloro-2-fluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine → N-(5-chloro-2-fluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

HRID 1046028ノート

反応式

HRID 1046028 の反応式
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][N:7]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[C:6](=[O:17])[C:5]=1[C:18](Cl)=[O:19])[CH3:2].[Cl:21][C:22]1[C:23]([O:30][C:31]2[CH:36]=[CH:35][N:34]=[CH:33][C:32]=2[C:37]2[CH:38]=[N:39][N:40]([CH3:42])[CH:41]=2)=[CH:24][C:25]([F:29])=[C:26]([NH2:28])[CH:27]=1>C(Cl)Cl.N1C=CC=CC=1>[Cl:21][C:22]1[C:23]([O:30][C:31]2[CH:36]=[CH:35][N:34]=[CH:33][C:32]=2[C:37]2[CH:38]=[N:39][N:40]([CH3:42])[CH:41]=2)=[CH:24][C:25]([F:29])=[C:26]([NH:28][C:18]([C:5]2[C:6](=[O:17])[N:7]([C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)[CH:8]=[CH:9][C:4]=2[O:3][CH2:1][CH3:2])=[O:19])[CH:27]=1

参加物

5

反応物 2

HCID 674688535-chloro-2-fluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamineHCID 866675054-Ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carbonyl chloride

生成物 1

HCID 54596551N-(5-chloro-2-fluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide収率 37.7%

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of 4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carbonyl chloride (0.275 g, 0.929 mmol) in CH2Cl2 (2 mL) was added a suspension of 5-chloro-2-fluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine (0.148 g, 0.464 mmol) in pyridine (2.00 mL) at 0° C. The resultant mixture was stirred at ambient temp for 30 min. The solvent was completely evaporated and the residue was stirred in water. The precipitate was collected by filtration and was re-crystallized from acetonitrile to provide N-(5-chloro-2-fluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (0.101 g, 37.6% yield) as an off-white solid. The mesylate salt was prepared by treatment with one equivalent of methanesulfonic acid. 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 9.20 (s, 1H), 8.62 (d, J=5.5 Hz, 1H), 8.51 (m, 1H), 8.47 (s, 1H), 8.23 (s, 1H), 8.00 (d, J=8.0 Hz, 1H), 7.75 (d, J=11 Hz, 1H), 7.50 (m, 2H), 7.41 (m, 2H), 7.25 (d, J=2.5 Hz, 1H), 6.60 (d, J=5.5 Hz, 1H), 4.30 (q, J=6 Hz, 2H), 3.92 (s, 3H), 2.30 (s, 3H), 1.30 (t, J=6 Hz, 3H); MS (ESI) m/z: 578.2 (M+H+).

後処理

  1. customThe solvent was completely evaporated
  2. filtrationThe precipitate was collected by filtration
  3. customwas re-crystallized from acetonitrile

出典と根拠

ORDレコード
ord-897b7886b02f4161bc44ddb0fa9dafdc
出典データセット
uspto-grants-2013_10
特許番号
US08569319B2

反応ノート

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