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

HRID 15511Notes

Reaction equation

HRID 15511 reaction equation
[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.C1C=CC2N(O)N=NC=2C=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>[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]([NH:61][C:14]([C:10]2[C:9](=[O:17])[N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[CH:13]=[CH:12][CH:11]=2)=[O:16])=[CH:57][C:56]=1[F:62]

Participants

6

Reactant 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

Product 1

HCID 15983978N-(4-(6,7-Dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamideYield 36.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (45 mg, 0.19 mmol), HOBt (20 mg) and EDCI.HCl (80 mg, 0.31 mmol) in DMF (2.5 mL) was added 4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorobenzenamine (56 mg, 0.18 mmol) at rt, and the reaction mixture was stirred over the weekend at rt. It was directly purified by preparative HPLC to afford the product (35 mg, 30%) as a beige-colored TFA salt solid. 1H NMR (CD3OD) δ 12.21 (s, 1H), 8.60 (dd, 2H, J=9.9, 1.6 Hz), 8.01 (d, 1H, J=12.6 Hz), 7.90 (dd, 1H, J=7.6, 1.6 Hz), 7.74 (s, 1H), 7.45-7.37 (m, 5H), 7.24 (t, 2H, J=8.2 Hz), 6.89 (d, 1H, J=6.6 Hz), 6.65 (t, 1H, J=6.6 Hz), 4.03 (s, 3H), 4.00 (s, 3H); MS(ESI+) m/z 530.2 (M+H)+.

Workup

  1. customIt was directly purified by preparative HPLC

Sources & evidence

ORD record
ord-a935e42062b54cdcae610b1a30eb84cf
Source dataset
uspto-grants-2010_06
Patent number
US07732613B2

Reaction notes

Loading…