1-Hydroxybenzotriazole → tert-Butyl 4-((4-(2-fluoro-4-(1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamido)phenoxy)-6-methoxyquinolin-7-yloxy)methyl)piperidine-1-carboxylate

HRID 15521Notes

Reaction equation

HRID 15521 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.[NH2:40][C:41]1[CH:74]=[CH:73][C:44]([O:45][C:46]2[C:55]3[C:50](=[CH:51][C:52]([O:58][CH2:59][CH:60]4[CH2:65][CH2:64][N:63]([C:66]([O:68][C:69]([CH3:72])([CH3:71])[CH3:70])=[O:67])[CH2:62][CH2:61]4)=[C:53]([O:56][CH3:57])[CH:54]=3)[N:49]=[CH:48][CH:47]=2)=[C:43]([F:75])[CH:42]=1>CN(C=O)C>[F:75][C:43]1[CH:42]=[C:41]([NH:40][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:74]=[CH:73][C:44]=1[O:45][C:46]1[C:55]2[C:50](=[CH:51][C:52]([O:58][CH2:59][CH:60]3[CH2:65][CH2:64][N:63]([C:66]([O:68][C:69]([CH3:72])([CH3:71])[CH3:70])=[O:67])[CH2:62][CH2:61]3)=[C:53]([O:56][CH3:57])[CH:54]=2)[N:49]=[CH:48][CH:47]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 210815271-(4-Fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acidHCID 59342474tert-Butyl 4-(((4-(4-amino-2-fluorophenoxy)-6-methoxyquinolin-7-yl)oxy)methyl)piperidine-1-carboxylate

Product 1

HCID 58833041tert-Butyl 4-((4-(2-fluoro-4-(1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamido)phenoxy)-6-methoxyquinolin-7-yloxy)methyl)piperidine-1-carboxylateYield 56.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (15 mg, 0.06 mmol), HOBt (10 mg) and EDCI.HCl (20 mg, 0.10 mmol) in DMF (2 mL) was added a solution of tert-butyl 4-((4-(4-amino-2-fluorophenoxy)-6-methoxyquinolin-7-yloxy)methyl)piperidine-1-carboxylate (35 mg, 0.07 mmol) in DMF (1 mL) at rt, and the reaction mixture was stirred overnight at rt. It was directly purified by preparative HPLC to afford the product (24 mg, 56%) as a white TFA salt solid. 1H NMR (CDCl3) δ 12.16 (s, 1H), 8.75 (d, 1H, J=7.7 Hz), 8.64 (d, 1H, J=5.5 Hz), 8.05 (d, 1H, J=12.1 Hz), 7.83 (s, 1H), 7.67-7.24 (m, 8H), 6.72 (d, 1H, J=6.1 Hz), 6.65 (t, 1H, J=6.6 Hz), 4.22-4.11 (m, 2H), 4.07 (s, 3H), 3.48 (s, 2H), 2.78 (m, 2H), 2.13 (m, 1H), 1.87 (m, 2H), 1.47 (s, 9H), 1.35 (m, 2H).

Workup

  1. customIt was directly purified by preparative HPLC

Sources & evidence

ORD record
ord-a5997787bb4942fc88b0497ceb0e3729
Source dataset
uspto-grants-2010_06
Patent number
US07732613B2

Reaction notes

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