反应详情

温度

45 °C

To a flask fitted with overhead stirrer, condenser, thermometer and nitrogen line was added 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]benzoic acid (1.0 eq), and acetonitrile (10 vols) followed by pyridine (3 eq) under a nitrogen atmosphere. Thionyl chloride (1.2 eq) as a solution in acetonitrile (0.225 vols) was added slowly, drop-wise via syringe pump over at least 2 hours. 5-Methylpyrazin-2-amine (1.2 eq) was added to the mixture as a solid. After 2.5 hours the reaction was quenched by adding toluene (10 vols) and 1.0M sodium carbonate solution (2.5 eq). The layers were separated. The organic layer was retained in the flask, then 1.0M hydrochloric acid (1.94 eq) was added. The mixture was agitated for 15 minutes then separated. The organic layer was washed with two aliquots of water (5 vols) then the solvent was removed on the rotary evaporator. Toluene (5 vols) was added to the residue, and warmed to 45° C. Isohexane (1.7 vols) was added, the mixture was seeded, and allowed to cool to ambient temperature overnight. The mixture was cooled to 0° C. for 4 hours, and then cooled to −10° C. for 3 hours. The solid was isolated by filtration then washed with isohexane (2.5 vols). After drying in the vacuum oven at 40° C. overnight, the desired product was obtained as a solid (corrected yield 85%).

1. customTo a flask fitted with overhead stirrer, condenser
2. customdrop-wise via syringe
3. waitpump over at least 2 hours
4. customAfter 2.5 hours the reaction was quenched
5. customThe layers were separated
6. customthen separated
7. washThe organic layer was washed with two aliquots of water (5 vols)
8. customthe solvent was removed on the rotary evaporator
9. additionToluene (5 vols) was added to the residue
10. additionIsohexane (1.7 vols) was added
11. temperatureto cool to ambient temperature overnight
12. temperatureThe mixture was cooled to 0° C. for 4 hours
13. temperaturecooled to −10° C. for 3 hours
14. customThe solid was isolated by filtration
15. washthen washed with isohexane (2.5 vols)
16. customAfter drying in the vacuum oven at 40° C. overnight