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 1046028노트

반응식

HRID 1046028 반응식
[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

참가 물질

5

반응물 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

생성물 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-carboxamide수율 37.7%

시약·촉매·용매 2

HCID 1049Pyridine용매HCID 6344Dichloromethane용매

실험 절차

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+).

후처리

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

출처 및 근거

ORD 기록
ord-897b7886b02f4161bc44ddb0fa9dafdc
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08569319B2

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