1-Hydroxybenzotriazole → N-(4-(7-(Benzyloxy)-6-methoxyquinolin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

HRID 15516노트

반응식

HRID 15516 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([OH:16])=O)[C:9]2=[O:17])=[CH:4][CH:3]=1.[CH:18]1[CH:19]=[CH:20][C:21]2N(O)N=N[C:22]=2[CH:23]=1.CCN=C=NCCCN(C)C.Cl.[CH3:40][O:41][C:42]1[CH:43]=[C:44]2[C:49](=[CH:50][C:51]=1[O:52][CH3:53])[N:48]=[CH:47][CH:46]=[C:45]2[O:54][C:55]1[CH:60]=[CH:59][C:58]([NH2:61])=[CH:57][C:56]=1[F:62]>CN(C=O)C>[CH2:53]([O:52][C:51]1[CH:50]=[C:49]2[C:44]([C:45]([O:54][C:55]3[CH:60]=[CH:59][C:58]([NH:61][C:14]([C:10]4[C:9](=[O:17])[N:8]([C:5]5[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=5)[CH:13]=[CH:12][CH:11]=4)=[O:16])=[CH:57][C:56]=3[F:62])=[CH:46][CH:47]=[N:48]2)=[CH:43][C:42]=1[O:41][CH3:40])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

참가 물질

6

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 114269974-((6,7-Dimethoxyquinolin-4-yl)oxy)-3-fluorobenzenamineHCID 210815271-(4-Fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid

생성물 1

HCID 58833040N-(4-(7-(Benzyloxy)-6-methoxyquinolin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide수율 64.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

To a mixture of 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (74 mg, 0.32 mmol), HOBt (16 mg) and EDCI.HCl (65 mg, 0.34 mmol) in DMF (3 mL) was added a solution of 4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorobenzenamine (120 mg, 0.31 mmol) in DMF (3 mL) at rt, and the reaction mixture was stirred overnight at rt. It was directly purified by preparative HPLC to afford the product (46 mg, 20%) as a white TFA salt solid. 1H NMR (DMF-d7) δ 12.22 (s, 1H), 8.71 (d, 1H, J=6.0 Hz), 8.59 (d, 1H, J=7.2 Hz), 8.14-7.31 (m, 15H), 6.84 (d, 1H, J=5.5 Hz), 6.72 (t, 1H, J=7.2 Hz), 5.35 (s, 2H), 4.02 (s, 3H); MS(ESI+) m/z 606.3 (M+H)+.

후처리

  1. customIt was directly purified by preparative HPLC

출처 및 근거

ORD 기록
ord-21800dd0b62449349295126bfd11879b
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07732613B2

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