反应详情

methyl (3-amino-4-fluoro-5-(4-methylpiperazin-1-yl)phenyl)(4-methoxybenzyl)carbamate (50 mg, 0.093 mmol), 4-(cyclopropyl(4-methoxybenzyl)amino)-2-(methylsulfonyl)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (44.6 mg, 0.112 mmol) and Cs2CO3 (91 mg, 0.280 mmol) in DMF (1 ml) were heated at 45° C. for 14 hours. LCMS showed product formation (m/e+=721, [M+H]+). The mixture was poured onto a Phenomenex Strata XC cation exchange resin (2 g adsorbent). The cartridge was washed with MeOH and CH3CN. The product was eluted with a 1:1 mixture of CH3CN and a 2 molar solution of NH3 in MeOH. Evaporation to dryness gave crude methyl (3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)-4-fluoro-5-(4-methylpiperazin-1-yl)phenyl)(4-methoxybenzyl)carbamate (69.5 mg). The material was used in the following PMB deprotection reaction without further purification.

1. additionThe mixture was poured onto a Phenomenex Strata XC cation exchange resin (2 g adsorbent)
2. washThe cartridge was washed with MeOH and CH3CN
3. washThe product was eluted with a 1:1 mixture of CH3CN
4. customEvaporation to dryness