反应详情

温度

50 °C

Combine 6-(1-methyl-piperidin-4-yloxy)-pyridin-2-ylamine (preparation 60, 200 mg, 0.96 mmol), and dioxane (15 mL), stir and heat at 50° C. Add 2-chloro-6-fluorobenzoyl chloride (214 □L, 1.1 mmol), and heat at 85° C. for an additional 3 hr. Cool the reaction to room temperature, and load onto a 5 g SCX cartridge. Wash resin with Methanol, then remove product with 2 M NH3/methanol. Concentrate in vacuo, and silica gel chromatography eluting with 5-20% 2 M NH3 in methanol/methylene dichloride. Dissolve the purified oil (286 mg, 81% isolated yield) in methanol, add NH4Cl (42 mg, 1 eq) as a solid, and sonicate the solution at room temperature for 15 min. Concentration in vacuo provides the title compound: mass spectrum (ion spray): m/z=364.1 (M+1); mp=139.6° C.

1. temperatureCool
2. customthe reaction to room temperature
3. concentrationConcentrate in vacuo, and silica gel chromatography
4. washeluting with 5-20% 2 M NH3 in methanol/methylene dichloride
5. dissolutionDissolve
6. customthe purified oil (286 mg, 81% isolated yield) in methanol
7. customsonicate the solution at room temperature for 15 min
8. concentrationConcentration in vacuo