Hydrochloric Acid → Azd-8330

Temperature

50 °C

A mixture of 2-(2-fluoro-4-iodophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid (2-vinyloxy-ethoxy)-amide (500 mg, 915 μmol) and hydrogen chloride (1 mL) in tetrahydrofuran (5 mL) was stirred overnight. Sodium hydroxide (1M, 2.00 mL) was then added, and after a further 10 minutes methyl isobutyl ketone (3 mL) and ethyl acetate (3 mL) were added to the mixture. The layers were separated and the organic solution was washed with 50% brine (4 mL), then evaporated (approximately half the material was lost by spillage). The residue was taken up in methyl isobutyl ketone (3 mL) and ethyl acetate (1 mL) and the mixture was heated to reflux. Upon cooling to 50° C. the mixture went cloudy and isohexane (5 mL) was added. This caused solid to crystallize and the mixture was cooled to 20° C., followed by a further addition of isohexane (5 mL). The solid was then filtered, washed with isohexane (1 mL) and dried in a vacuum oven at 40° C., to provide the title compound, 140 mg.

1. customThe layers were separated
2. washthe organic solution was washed with 50% brine (4 mL)
3. customevaporated (approximately half the material
4. temperatureethyl acetate (1 mL) and the mixture was heated to reflux
5. additionwas added
6. customThis caused solid to crystallize
7. temperaturethe mixture was cooled to 20° C.
8. additionfollowed by a further addition of isohexane (5 mL)
9. filtrationThe solid was then filtered
10. washwashed with isohexane (1 mL)
11. customdried in a vacuum oven at 40° C.

ORD record

ord-cb894112e7a64dec81fdb45d9072a6e0

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08299076B2