Methanesulfonic Acid → N-(3-bromo-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine

温度

105 °C

To a solution of 3-bromo-5-methylaniline (45.77 g, 246 mmol) in toluene (500 ml) were sequentially added 2-chloro-4-(trifluoromethyl)pyrimidine (53.9 g, 295 mmol) and methanesulfonic acid (28.4 g, 295 mmol). The resulting solution was heated to 105° C. overnight. The resulting mixture was cooled, diluted with water (500 mL) and adjusted to pH 14 via addition of a concentrated aqueous sodium hydroxide solution (26.6 g of a solution containing 320 mmol of sodium hydroxide). The resulting solution was extracted with MTBE (500 mL), the layers separated, and the organic layer subsequently washed with water (300 ml) then 50% saturated brine solution (200 mL). The organic layer was concentrated in vacuo to 200 ml resulting in product crystallization. To the slurry was added heptane (660 mL) over 40 minutes followed by a 2 hr aging at 20° C. The solid was isolated via filtration, washed with heptane (200 mL) and dried in a vacuum oven at 40° C. overnight to provide the title compound (69.5 g, 209 mmol) as a light yellow solid. MS ESI: [M+H]+ m/z 334.0. 1H NMR (400 MHz, CDCl3): δ 8.68 (d, J=4.9 Hz, 1H); 7.79 (s, 1H); 7.30 (s, 2H); 7.10-7.06 (m, 2H); 2.36 (s, 3H).

1. temperatureThe resulting mixture was cooled
2. extractionThe resulting solution was extracted with MTBE (500 mL)
3. customthe layers separated
4. washthe organic layer subsequently washed with water (300 ml)
5. concentrationThe organic layer was concentrated in vacuo to 200 ml
6. customresulting in product crystallization
7. customaging at 20° C
8. customThe solid was isolated via filtration
9. washwashed with heptane (200 mL)
10. customdried in a vacuum oven at 40° C. overnight

ORDレコード

ord-3c00fcb95e754dd8a59a3760d358bfbe

出典データセット

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08551984B2