Kinase Growth Factor VEGFR-2 and FGFR-1 Inhibitors

Kinase Growth Factor VEGFR-2 and FGFR-1 Inhibitors 

Bhide et al, US Patent 6,969,717 (November 29, 2005) Assignee Bristol-Myers Squibb Company Utility Antiangiogenic Agents in the Treatment of Cancer 

Preparation of 5-methyl-4-(lH-pyrrolo[2,3-b]pyridin-5-yloxy)-pyrrolo [2,l-f][l,2,4]triazine-6-carboxylic acid ethyl ester 

Sodium hydride (0.36 mmol) was added to 5-hydroxy-7-azaindole (0.36 mmol) dissolved in 1.5 ml DMF at 0°C, then treated with 4-chloro-5-methylpyrrolo[2,l-f] [l,2,4]triazine-6-carboxylic acid ethyl ester (0.32mmol), and stirred 16 hours at ambient temperature. The reaction was quenched with 20 ml saturated NH4C1 solution, then extracted three times with 25 ml EtOAc, and the extract washed with 50 ml brine. The solution was dried, then concentrated, and the residue purified by preparative HPLC, RT = 7.12 minute. 

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Pyrrolotriazine inhibitors, (HI), prepared by Hunt (5) inhibited tyrosine kinase activity in VEGFR-2, FGFR-1, PDGFR, HER-1, and HER-2 growth factor receptors. 

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