Diisopropylethylamine → N-(bicyclo[1.1.1]pentan-1-yl)-5-bromo-4-(methylthio)pyrimidin-2-amine

Temperature

100 °C

To a stirring solution of 5-bromo-2-chloro-4-(methylthio)pyrimidine (1.0 g, 4.18 mmol) in NMP (10.0 mL) was added bicyclo[1.1.1]pentan-1-amine hydrochloride (749 mg, 6.26 mmol, prepared according to Org. Lett., 13(17): 4746-4748 (2011)) and DIEA (2.19 mL, 12.53 mmol). The mixture was stirred at 100° C. for 16 h and then the solvent was removed under reduced pressure. The residue was diluted in 100 mL ethyl acetate and 50 mL 1M aqueous solution of sodium hydrogen phosphate. The layers were separated and the aqueous layer was extracted with 50 mL ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to afford N-(bicyclo[1.1.1]pentan-1-yl)-5-bromo-4-(methylthio)pyrimidin-2-amine (1250 mg, 4.37 mmol, 105% yield) as a solid that was used without further purification. MS (ESI) m/z 286.0 [M+1]+ and 288.0 [M+H]+.

1. customthe solvent was removed under reduced pressure
2. additionThe residue was diluted in 100 mL ethyl acetate
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with 50 mL ethyl acetate
5. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure

ORD record

ord-b13e6352d6374b8382272a0708efc6f2

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09139534B2