Dimethylformamide → 5-bromo-2-chloro-3-methylpyrimidin-4(3H)-one

To a solution of 5-bromo-2-chloropyrimidin-4(3H)-one (1.00 g, 4.78 mmol) in DME (12 mL)/DMF (3 mL) under N2 at 0° C. was added LiH (0.044 g, 5.25 mmol), and the reaction mixture was stirred for 15 minutes at room temperature. Iodomethane (0.589 mL, 9.45 mmol) was then added and the reaction mixture was stirred at room temperature for 30 minutes and then at 60° C. for 1.5 hours. The reaction mixture was quenched with H2O and then partitioned between EtOAc and saturated aqueous NaCl. The phases were separated, and the aqueous phase was re-extracted with EtOAc (1×). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude yellow oil. The crude product was purified by flash column chromatography, eluting with 25:1 dichloromethane/EtOAc. The desired product (0.764 g, 72%) was obtained as a yellow crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ 8.26 (s, 1H), 3.59 (s, 3H). LRMS (ESI pos) m/e 223, 225 (M+1, Br pattern).

1. stirringthe reaction mixture was stirred at room temperature for 30 minutes
2. waitat 60° C. for 1.5 hours
3. customThe reaction mixture was quenched with H2O
4. custompartitioned between EtOAc and saturated aqueous NaCl
5. customThe phases were separated
6. extractionthe aqueous phase was re-extracted with EtOAc (1×)
7. dry with materialThe combined organic layers were dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customto yield a crude yellow oil
11. customThe crude product was purified by flash column chromatography
12. washeluting with 25:1 dichloromethane/EtOAc

ORD record

ord-e33cb68a39f24c199a5b9745fb3f7201

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07723330B2