1-Hydroxybenzotriazole → N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxamide

HRID 2237246Notes

Reaction equation

HRID 2237246 reaction equation
[O:1]=[C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=[CH:4][N:3]1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.C(OC1C=[CH:51][C:50]([NH:53][C:54]2[N:59]=CN=[C:56]([O:60][C:61]3[CH:66]=[CH:65][C:64]([NH:67]C(=O)CC(NC4C=CC(F)=CC=4)=O)=[CH:63][C:62]=3[F:81])[CH:55]=2)=CC=1)C1C=CC=CC=1>CN(C=O)C>[NH2:59][C:54]1[CH:55]=[C:56]([O:60][C:61]2[CH:66]=[CH:65][C:64]([NH:67][C:8]([C:7]3[C:2](=[O:1])[N:3]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=4)[CH:4]=[CH:5][CH:6]=3)=[O:10])=[CH:63][C:62]=2[F:81])[CH:51]=[CH:50][N:53]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 210815852-Oxo-1-phenyl-1,2-dihydropyridine-3-carboxylic acidHCID 59853038N-(4-(6-(4-(Benzyloxy)phenylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide2×

Product 1

HCID 46852003N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxamideYield 45.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxylic acid (36 mg, 0.17 mmol) and HOBt (18 mg) in DMF (3 mL) at rt was added EDCI.HCl (45 mg, 0.23 mmol) followed by 4-(4-amino-2-fluorophenoxy)pyridine-2-amine (Compound B of Example 24, 36 mg, 0.17 mmol), and the reaction mixture was stirred at rt overnight. Purification of the reaction mixture by preparative HPLC afforded the title compound (32 mg, 36%) as a beige colored solid (TFA salt). 1H NMR (DMSO-d6) δ 13.35 (br s, 1H), 12.11 (s, 1H), 8.52 (dd, 1H, J=7.3, 2.1 Hz), 8.08 (dd, 1H, J=6.6, 2.1 Hz), 8.03 (d, 1H, J=2.3 Hz), 7.89 (d, 1H, J=7.2 Hz), 7.81 (s, 1H), 7.54-7.36 (m, 6H), 6.69-6.63 (m, 2H), 6.08 (d, 1H, J=2.4 Hz), 3.55 (br s, 1H); MS(ESI+) m/z 417.2 (M+H)+.

Workup

  1. customPurification of the reaction mixture by preparative HPLC

Sources & evidence

ORD record
ord-a36b55385906485aba1bfd95b37730d7
Source dataset
uspto-grants-2010_05
Patent number
US07714138B2

Reaction notes

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