Butyl iodide → 2-Butylamino-4-chloro-6-methylpyrimidine

Temperature

0 °C

To 2-amino-4-chloro-6-methylpyrimidine (10.0 g, 69.7 mmol) dissolved in 70 mL of anhydrous tetrahydrofuran was added 21 mL (2.5 equilvalents) of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) at ambient temperature. The solution was cooled to ~10° C. and 69.6 mL (1.0 equivalent) of 1M lithium hexamethyldisilazide in tetrahydrofuran was added. The solution was stirred at 0° C. for 30 minutes and then 7.92 mL (1.0 equivalent) of 1-iodobutane was added at 0° C., and the reaction was allowed to warm to ambient temperature. The reaction mixture was poured into ethyl acetate and washed with water (2×); the aqueous washes were back-extracted with ethyl acetate (2×). The combined organic extracts were dried over potassium carbonate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with 13% ethyl acetate in hexane to afford 4.6 g (33%) of the title compound. 1H NMR (CDCl3, 300 MHz) δ 0.93 (t, 3H), 1.40 (m, 2H), 1.57 (m, 2H), 2.30 (s, 3H), 3.41 (m, 2H), 5.12 (bs, 1H), 6.43 (s, 1H). MS (DCl/NH3) m/e 200 (M+H)+.

1. temperatureThe solution was cooled to ~10° C.
2. temperatureto warm to ambient temperature
3. washwashed with water (2×)
4. extractionthe aqueous washes were back-extracted with ethyl acetate (2×)
5. dry with materialThe combined organic extracts were dried over potassium carbonate
6. concentrationconcentrated in vacuo
7. customThe residue was purified by flash chromatography on silica gel eluting with 13% ethyl acetate in hexane

ORD record

ord-4eedc480b68c48b09a64eb6021466700

Source dataset

uspto-grants-1993_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05250548