3,5-Dimethyl-4-hydroxybenzonitrile → N-[5-bromo-6-(4-cyano-2,6-dimethylphenoxy)-2-(4-cyano-phenylamino)pyrimidin-4-yl]benzamide

Temperature

73 °C

1300 ml of dimethylformamide was added to a RB flask, to this was added 54 g of 3,5-dimethyl-4-hydroxybenzonitrile, 51.38 g of dimethyl amino pyridine, 68.30 g of diazabicyclo undecene and 150 g of N-[5-bromo-6-chloro-2-(4-cyanophenylamino)-pyrimidin-4-yl]-benzamide at 27±3° C. The reaction mixture was heated to 73±2° C. and maintained at the same for 5 hrs. The reaction mixture was cooled to 27±3° C. and filtered. The filtrate was taken into an RB flask to which was added 300 ml of IPA and stirred for 30 mins. 3000 ml of water was taken in another RB flask and the reaction mass added. The reaction mass was heated to 47±3° C., stirred, cooled to 42±3° C. and filtered hot. The solid was washed with water and suck dried at 27±3° C. The solid was further washed with 150 ml of IPA and the wet cake was charged into a clean RB flask. To this was added 1500 ml of dimethyl formamide and heated to 47±3° C. To the reaction mass was slowly added 3000 ml of water with continued stirring, followed by cooling the reaction mass to 27±3° C. The reaction mass was filtered, and the solid was washed with water followed by IPA. The solid was then dried under vacuum to yield the title compound.

1. temperaturemaintained at the same for 5 hrs
2. temperatureThe reaction mixture was cooled to 27±3° C.
3. filtrationfiltered
4. customThe filtrate was taken into an RB flask to which
5. additionwas added 300 ml of IPA
6. additionthe reaction mass added
7. temperatureThe reaction mass was heated to 47±3° C.
8. stirringstirred
9. temperaturecooled to 42±3° C.
10. filtrationfiltered hot
11. washThe solid was washed with water and suck
12. customdried at 27±3° C
13. washThe solid was further washed with 150 ml of IPA
14. additionthe wet cake was charged into a clean RB flask
15. additionTo this was added 1500 ml of dimethyl formamide
16. temperatureheated to 47±3° C
17. temperatureby cooling the reaction mass to 27±3° C
18. filtrationThe reaction mass was filtered
19. washthe solid was washed with water
20. customThe solid was then dried under vacuum

ORD record

ord-93d8e63815e840de9cb681ce382add7d

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653266B2