Methyl iodide → ethyl 2-[4-methyl-6-oxopyridazin-1(6H)-yl]propanoate

Temperature

-78 °C

To ethyl [4-methyl-6-oxopyridazin-1(6H)-yl]acetate (0.132 g, 0.673 mmol) in tetrahydrofuran (4 mL) at −78° C. was added 1M lithium hexamethyldisilazane solution (0.74 mL). The reaction mixture was stirred at −78° C. for 15 min then was added methyl iodide (0.046 mL, 0.74 mmol). After being stirred at −78° C. for 2 h, the reaction mixture was allowed to warm to ambient temperature over 0.5 h. Removal of the volatiles in vacuo followed by purification using a Biotage Horizon® system (0-50% ethyl acetate/hexanes mixture) gave ethyl 2-[4-methyl-6-oxopyridazin-1(6H)-yl]propanoate as oil. To 88 mg (0.42 mmol) of the above oil in tetrahydrofuran (0.3 mL), water (0.2 mL) and methanol (0.2 mL) was added 5 N sodium hydroxide solution (0.2 mL). The reaction mixture was stirred at ambient temperature for 3 h then neutralized with 2 N hydrochloric acid and purified by reverse phase HPLC (TMC Pro-Pac C18; 0-40% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient). Removal of the volatiles in vacuo afforded the title compound as a white solid. LC/MS 183.2 (M+1).

1. stirringAfter being stirred at −78° C. for 2 h
2. temperatureto warm to ambient temperature over 0.5 h
3. customRemoval of the volatiles in vacuo
4. customfollowed by purification

ORD record

ord-0092e2a7708e4ab199a23b61702a7b3c

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653260B2