1-Hydroxybenzotriazole → N-(4-(1H-Pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorophenyl)-2-oxo-5-phenyl-1,2-dihydropyridine-3-carboxamide

HRID 347538Notes

Reaction equation

HRID 347538 reaction equation
[O:1]=[C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][C:5]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:4][NH:3]1.C1C=CC2N(O)N=NC=2C=1.[CH3:27][CH2:28][N:29]=[C:30]=[N:31][CH2:32][CH2:33][CH2:34]N(C)C.Cl.Cl.Cl.[F:41][C:42]1[CH:43]=[C:44]([NH:69]C(NC(=O)CC2C=CC(F)=CC=2)=S)[CH:45]=[CH:46][C:47]=1[O:48][C:49]1C2=C(C)C(OCCN3CCN(C)CC3)=CN2N=CN=1>CN(C=O)C>[NH:31]1[C:30]2=[N:29][CH:28]=[CH:27][C:49]([O:48][C:47]3[CH:46]=[CH:45][C:44]([NH:69][C:8]([C:7]4[C:2](=[O:1])[NH:3][CH:4]=[C:5]([C:11]5[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=5)[CH:6]=4)=[O:10])=[CH:43][C:42]=3[F:41])=[C:34]2[CH:33]=[CH:32]1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 103759752-Hydroxy-5-phenylnicotinic acidHCID 1317262361-(3-Fluoro-4-(5-methyl-6-(2-(4-methylpiperazin-1-yl)ethoxy)pyrrolo[2,1-f][1,2,4] triazin-4-yloxy)phenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea, bis-hydrochloride salt2×

Product 1

HCID 21081773N-(4-(1H-Pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorophenyl)-2-oxo-5-phenyl-1,2-dihydropyridine-3-carboxamideYield 22.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-oxo-5-phenyl-1,2-dihydropyridine-3-carboxylic acid (35 mg, 0.16 mmol), HOBT (25 mg), and EDCI.HCl (80 mg, 0.42 mmol) in DMF (3.0 mL) at room temperature was added 4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorobenzenamine (30 mg, 0.12 mmol, Compound B of Example 132). The mixture was stirred at room temperature overnight and concentrated in vacuo. The residue was purified by preparative HPLC to afford the desired product (12 mg, 13%) as a light brown solid. 1H NMR (CD3OD) δ 8.81 (d, 1H, J=2.8 Hz), 8.17 (d, 1H, J=6.6 Hz), 8.00 (dd, 1H, J=12.6, 2.2 Hz), 7.94 (d, 1H, J=3.3 Hz), 7.52–7.27 (m, 7H), 6.80 (d, 1H, J=9.3 Hz), 6.72 (d, 1H, J=6.6 Hz), 6.54 (d, 1H, J=3.8 Hz); MS(ESI+) m/z 441.1 (M+H)+.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-8074c9d8a0ca48cfa8b7165ea1ddd980
Source dataset
uspto-grants-2007_02
Patent number
US07173031B2

Reaction notes

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