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

HRID 2117173Notes

Reaction equation

HRID 2117173 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[C:12]([N+:14]([O-:16])=[O:15])[CH:11]=[C:10]([C:17]([OH:19])=O)[C:9]2=[O:20])=[CH:4][CH:3]=1.Cl.Cl.[F:23][C:24]1[CH:25]=[C:26]([NH:51]C(NC(=O)CC2C=CC(F)=CC=2)=S)[CH:27]=[CH:28][C:29]=1[O:30][C:31]1[C:36]2=[C:37]([CH3:50])C(OCCN3CCN(C)CC3)=CN2N=CN=1.CN([P+](ON1N=[N:83][C:78]2[CH:79]=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.[CH2:92]([N:94](CC)CC)C>CN(C=O)C.O>[NH:94]1[C:92]2=[N:83][CH:78]=[CH:79][C:31]([O:30][C:29]3[CH:28]=[CH:27][C:26]([NH:51][C:17]([C:10]4[C:9](=[O:20])[N:8]([C:5]5[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=5)[CH:13]=[C:12]([N+:14]([O-:16])=[O:15])[CH:11]=4)=[O:19])=[CH:25][C:24]=3[F:23])=[C:36]2[CH:37]=[CH:50]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 210815281-(4-Fluorophenyl)-5-nitro-2-oxo-1,2-dihydropyridine-3-carboxylic 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 21081764N-(4-(1H-Pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-5-nitro-2-oxo-1,2-dihydropyridine-3-carboxamideYield 76%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-(4-fluorophenyl)-5-nitro-2-oxo-1,2-dihydropyridine-3-carboxylic acid (40 mg, 0.14 mmol) and 4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorobenzenamine (35 mg, 0.14 mmol, Compound B of Example 132) in DMF (1 mL) was stirred with BOP reagent (100 mg, 0.23 mmol) and triethylamine (0.1 mL) at 50° C. for 1 h. The reaction mixture was cooled to room temperature and diluted with water. The solid that formed was collected, washed with aqueous sodium bicarbonate solution, 1 N HCl solution, and water to afford the title compound (54 mg, 76%). 1H NMR (DMSO-d6) δ 12.19 (s, 1H), 11.04 (s, 1H), 9.37 (d, 1H, J=2.6 Hz), 9.03 (d, 1H, J=2.6 Hz), 8.18 (d, 1H, J=5.5 Hz), 8.01 (dd, 1H, J=10.2, 2.6 Hz), 7.71 (m, 2H), 7.61 (m, 1 H), 7.46 (m, 4H), 6.55 (d, 1H, J=5.5 Hz), 6.36 (s, 1 Hz); MS(ESI+) m/z 504 (M+H)+.

Workup

  1. customThe solid that formed
  2. customwas collected
  3. washwashed with aqueous sodium bicarbonate solution, 1 N HCl solution, and water

Sources & evidence

ORD record
ord-a53e1c426f08425c9275f44139cb7f50
Source dataset
uspto-grants-2008_10
Patent number
US07439246B2

Reaction notes

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