Cesium carbonate → 3-Chloro-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)benzonitrile

Temperatur

100 °C

A mixture of 2-chloro-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine (211 mg, 1 mmol), 4-amino-3-chlorobenzonitrile (305 mg, 2 mmol), cesium carbonate (0.65 g, 2 mmol), XantPhos (17 mg, 0.03 mmol) and Pd2(dba)3 (5 mg, 0.02 mmol) in dioxane (3 mL) was sonnicated in an ultrasonic bath for 1 min. The mixture was then degassed under a stream of nitrogen for 5 min. The tube was sealed and the reaction was heated at 100° C. for 18 h. The reaction mixture was cooled and diluted with ethyl acetate (15 mL). The organic layer was washed with water (2×20 mL) and the combined aqueous extracts were further washed with ethyl acetate (2×15 mL). The combined organics were passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification of the residue via silica gel column chromatography (0-100% ethyl acetate/isohexane) gave 3-chloro-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)benzonitrile as a white solid (140 mg, 45%). 1H NMR (400 MHz, CDCl3): δ 8.85 (d, J=8.8, 1H); 8.23 (d, J=1.1, 1H); 7.80 (s, 1H); 7.68 (d, J=1.9, 1H); 7.58-7.53 (m, 1H); 5.32 (s br, 1H); 3.11 (d, J=4.7, 3H).

1. customThe mixture was then degassed under a stream of nitrogen for 5 min
2. customThe tube was sealed
3. temperatureThe reaction mixture was cooled
4. additiondiluted with ethyl acetate (15 mL)
5. washThe organic layer was washed with water (2×20 mL)
6. washthe combined aqueous extracts were further washed with ethyl acetate (2×15 mL)
7. customThe combined organics were passed through a phase separation cartridge
8. customthe solvent removed under reduced pressure
9. customPurification of the residue via silica gel column chromatography (0-100% ethyl acetate/isohexane)

ORD-Eintrag

ord-5bee55ddc08d4c47a94515cf5b1c2ba4

Quelldatensatz

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08791130B2