反应详情

温度

140 °C

To (5-fluoropyridin-2-yl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone from Example 1 (1 equiv) in 2-propanol are added cyclopropylamine (5 equiv) and 3 Å(8-12 mesh) molecular sieves, and the mixture is heated at 140° C. in a microwave reactor. Additional cyclopropylamine is added and microwave or conventional heating is continued until the reaction is substantially complete according to NMR. Then a suspension of sodium borohydride (10 equiv) in 2-propanol is added and the mixture is stirred at rt. Methanol, additional sodium borohydride, and traces of HOAc are added as necessary until the reaction is substantially complete, then the mixture is filtered and the filtrate is concentrated. DMSO is added and the mixture is purified by preparative HPLC to afford 2-((cyclopropylamino)(5-fluoropyridin-2-yl)methyl)-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine.

1. temperaturemicrowave or conventional heating
2. additionis added
3. filtrationthe mixture is filtered
4. concentrationthe filtrate is concentrated
5. additionDMSO is added
6. customthe mixture is purified by preparative HPLC