[4-(4-Amino-2-fluoro-phenoxy)-6,7-dimethoxy-quinolin-2-yl]-methyl-amine → N-(3-fluoro-4-{[2-(methylamino)-6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 2106166Notes

Reaction equation

HRID 2106166 reaction equation
[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH3:20])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[C:9]([NH:21][CH3:22])[CH:8]=2)=[C:4]([F:25])[CH:3]=1.COC1C=C2C(=CC=1OC)N=C(SC)C=C2OC1C=CC(N[C:50]([C:52]2([C:55]([NH:57][C:58]3[CH:63]=[CH:62][C:61]([F:64])=[CH:60][CH:59]=3)=[O:56])[CH2:54][CH2:53]2)=[O:51])=CC=1F>>[F:25][C:4]1[CH:3]=[C:2]([NH:1][C:50]([C:52]2([C:55]([NH:57][C:58]3[CH:63]=[CH:62][C:61]([F:64])=[CH:60][CH:59]=3)=[O:56])[CH2:54][CH2:53]2)=[O:51])[CH:24]=[CH:23][C:5]=1[O:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([O:19][CH3:20])=[C:14]([O:17][CH3:18])[CH:15]=2)[N:10]=[C:9]([NH:21][CH3:22])[CH:8]=1

Participants

3

Reactant 2

HCID 57810112[4-(4-Amino-2-fluoro-phenoxy)-6,7-dimethoxy-quinolin-2-yl]-methyl-amineHCID 57810395N-(4-{[6,7-bis(methyloxy)-2-(methylthio)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluoro-phenyl)cyclopropane-1,1-dicarboxamide

Product 1

HCID 57810280N-(3-fluoro-4-{[2-(methylamino)-6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Procedure

′N-(3-fluoro-4-{[2-(methylamino)-6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide was synthesized from [4-(4-amino-2-fluoro-phenoxy)-6,7-dimethoxy-quinolin-2-yl]-methyl-amine in a similar manner as N-(4-{[6,7-bis(methyloxy)-2-(methylthio)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-(4-fluoro-phenyl)cyclopropane-1,1-dicarboxamide. It was purified by preparatory HPLC using ammonium acetate and isolated as a white solid (6.0 mg, 4.0% yield). 1H NMR (DMSO-d6) δ 10.42 (s, 1H), 9.91 (s, 1H), 7.88 (dd, 1H), 7.56 (m, 2H), 7.44 (m, 4H), 7.09 (t, 2H), 5.90 (s, 1H), 3.88 (s, 3H), 3.85 (s, 3H), 3.39 (br s, 1H), 2.92 (s, 3H), 1.41 (dt, 4H). LCMS: m/z 535 (M+H)+.

Workup

  1. customIt was purified by preparatory HPLC

Sources & evidence

ORD record
ord-f193d97998e24ee0a81081402f08b5e3
Source dataset
uspto-grants-2009_08
Patent number
US07579473B2

Reaction notes

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