Acetic Acid → 2-(N-(2-bromo-4-(2-propyl)phenyl)-N-ethylamino)-4-(morpholinomethyl)-6-methylpyrimidine

A solution of N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-methyl-6-(4-morpholinylcarbonyl)-2-pyrimidinamine (750 mg, 1.72 mmol) in anhydrous THF (1.4 mL) was stirred at ambient temperature under a nitrogen atmosphere. A solution of borane in THF (1 M, 3.6 mL, 3.6 mmol) was added dropwise. The reaction mixture was then warmed to reflux temperature and stirred for 20 hours. After cooling to room temperature, acetic acid (3.5 mL) was added slowly and the mixture was heated to reflux temperature and stirred for 30 min. After being cooled to ambient temperature, the reaction mixture was poured onto a 3 N NaOH solution, mixed and extracted three times with EtOAc. The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. Column chromatography (EtOAc) of the residue afforded the title compound as an oil (300 mg, 39% yield, Rf 0.3): NMR (CDCl3, 300 MHz): d 7.5 (s, 1H), 7.2 (d, 1H, J=7), 7.15 (d, 1H, J=7), 6.5 (s, 1H), 4.3-4.1 (m, 1H), 3.8-3.6 (m, 7H), 3.5-3.3 (m, 2H), 2.9 (septet, 1H, J=7), 2.55-2.35 (br m, 3H), 2.35-2.25 (m, 2H), 1.3 (d, 6H, J=7), 1.2 (t, 3H, J=7); CI-HRMS: calcd: 4.33.1603 (M+H), found: 433.1586.

1. temperatureThe reaction mixture was then warmed
2. temperatureto reflux temperature
3. temperaturethe mixture was heated
4. temperatureto reflux temperature
5. stirringstirred for 30 min
6. temperatureAfter being cooled to ambient temperature
7. additionmixed
8. extractionextracted three times with EtOAc
9. dry with materialThe combined organic layers were dried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD record

ord-f4cffd6c8c594c38829c35f5a7fc82cb

Source dataset

uspto-grants-2000_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06107301