反应详情

温度

120 °C

6-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one (Step A) (568 kg, 1.00 mol eq) is mixed with 3,4,5-trimethoxyaniline (402 kg, 1.25 mol eq) in N-methylpyrrolidin-2-one (2835 kg) with stirring under a nitrogen atmosphere. To this is added water (11 kg) and the mixture heated to about 120° C. and stirred for about 10 hours. This is then cooled to about 65° C. and the pH adjusted to pH 8.5 with 4% w/w aqueous sodium hydroxide solution. The resulting slurry is further cooled to about 20° C., stirred for at least 6 hours and then filtered. The filtered solid is washed twice with water (2×1440 kg) then twice with acetone (2×1140 kg) and finally dried under vacuum at about 40° C. to give the title compound (754 kg, 91%) as a colored solid.

1. stirringstirred for about 10 hours
2. temperatureThis is then cooled to about 65° C.
3. temperatureThe resulting slurry is further cooled to about 20° C.
4. stirringstirred for at least 6 hours
5. filtrationfiltered
6. washThe filtered solid is washed twice with water (2×1440 kg)
7. dry with materialtwice with acetone (2×1140 kg) and finally dried under vacuum at about 40° C.