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

HRID 445517Notes

Reaction equation

HRID 445517 reaction equation
[NH2:1][C:2]1[CH:23]=[CH:22][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]([NH2:21])[CH:8]=2)=[C:4]([F:24])[CH:3]=1.COC1C=C2C(=CC=1OC)N=C(SC)C=C2OC1C=CC(N[C:49]([C:51]2([C:54]([NH:56][C:57]3[CH:62]=[CH:61][C:60]([F:63])=[CH:59][CH:58]=3)=[O:55])[CH2:53][CH2:52]2)=[O:50])=CC=1F>>[NH2:21][C:9]1[CH:8]=[C:7]([O:6][C:5]2[CH:22]=[CH:23][C:2]([NH:1][C:49]([C:51]3([C:54]([NH:56][C:57]4[CH:62]=[CH:61][C:60]([F:63])=[CH:59][CH:58]=4)=[O:55])[CH2:53][CH2:52]3)=[O:50])=[CH:3][C:4]=2[F:24])[C:16]2[C:11](=[CH:12][C:13]([O:19][CH3:20])=[C:14]([O:17][CH3:18])[CH:15]=2)[N:10]=1

Participants

3

Reactant 2

HCID 578103564-(4-Amino-2-fluoro-phenoxy)-6,7-dimethoxy-quinolin-2-ylamineHCID 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 57810129N-(4-{[2-amino-6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Procedure

N-(4-{[2-amino-6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide was synthesized from 4-(4-amino-2-fluoro-phenoxy)-6,7-dimethoxy-quinolin-2-ylamine in a similar manner as N-(4-{[6,7-bis(methyloxy)-2-(methylthio)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide. It was purified by preparatory HPLC using ammonium acetate and isolated as a white solid (4.0% yield). 1H NMR (DMSO-d6) δ 10.34 (s, 1H), 9.95 (s, 1H), 7.82 (d, 1H), 7.58 (m, 2H), 7.44 (d, 1H), 7.33 (t, 1H), 7.25 (s, 1H), 7.09 (t, 2H), 7.07 (s, 1H), 6.17 (br s, 2H), 5.66 (s, 1H), 3.79 (s, 3H), 3.77 (s, 3H), 1.40 (d, 4H). LCMS: m/z 535 (M+H)+.

Workup

  1. customIt was purified by preparatory HPLC

Sources & evidence

ORD record
ord-a5d10672c57b4a0dba46229d7dee862f
Source dataset
uspto-grants-2013_07
Patent number
US08476298B2

Reaction notes

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