Dimethyl malonate → HCID 57613442, compound

Temperature

80 °C

To a suspension of NaH (1.98 g, 50 mmol, 60% in oil) in DMSO (20 mL) is added dimethyl malonate (5.67 mL, 50 mmol) at 23° C. (cooled by ice-water if necessary). After the evolution of hydrogen has ceased, 4-chloro-6-methylsulfanyl-pyrimidine 2 (3.22 g, 20 mmol) is added. The reaction is further heated at 80° C. for 5 hours. The reaction mixture is then cooled to room temperature, and quenched with saturated NH4Cl solution (50 mL). The organics are extracted with ethyl acetate (3×60 mL). The combined organic layers are washed with brine (2×) and dried over Na2SO4, filtered and concentrated. 50 mL of hexanes are added to the residue and heated at 60° C. for half hour and then cooled to room temperature. The solid is filtered and washed with hexanes to afford 2-(6-methylsulfanyl-pyrimidin-4-yl)-malonic acid dimethyl ester. (If necessary, the hexanes washing can be concentrated and purified by silica gel flash chromatography eluting with ethyl acetate in hexanes from 0% to 40% to afford additional product). 1H NMR 400 MHz (DMSO-d6) Compound A δ 8.92 (s, 1H), 7.53 (s, 1H), 5.20 (s, 1H) 3.70 (s, 6H), 2.56 (s, 3H); Compound B (tautomer of A, the structure is tentatively assigned) 8.37 (s, 1H), 7.34 (s, 1H), 3.66 (s, 6H), 2.48 (s, 3H).

1. temperatureThe reaction mixture is then cooled to room temperature
2. customquenched with saturated NH4Cl solution (50 mL)
3. extractionThe organics are extracted with ethyl acetate (3×60 mL)
4. washThe combined organic layers are washed with brine (2×)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. addition50 mL of hexanes are added to the residue
9. temperatureheated at 60° C. for half hour
10. temperaturecooled to room temperature
11. filtrationThe solid is filtered
12. washwashed with hexanes

ORD record

ord-e8619b67e28d48928354b041663bf5e0

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08026243B2