Dimethylformamide → 5-(2-Dimethylamino-vinyl)-pyrazine-2-carboxylic acid methyl ester

Temperature

90 °C

A solution of 5-methylpyrazine-2-carboxylic acid (5.0 g, 36.2 mmol), N,N-dimethylformamide dimethyl acetal (15 mL, 113 mmol) and N,N-dimethylformamide (15 mL) was heated with stirring in an oil-bath at 90° C. under argon for 60 min. The temperature of the oil-bath was raised to 120° C., and the heating and stirring continued for an additional 120 min. The reaction mixture was then cooled to 25° C. and concentrated in vacuo to a volume of about 10 mL. The oily residue was partitioned with water (50 mL) and ethyl acetate (50 mL). The aqueous phase was further extracted with ethyl acetate (2×50 mL), and each organic extract was washed with a portion of a saturated aqueous sodium chloride solution (25 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo to a dark oil. The residue was treated with a solution of diethyl ether/hexanes (50 mL, 3:2) to produce an orange solid. The solid was collected by filtration and washed with a mixture of diethyl ether/hexanes (25 mL, 1:1) to afford 5-(2-dimethylamino-vinyl)-pyrazine-2-carboxylic acid methyl ester (4.94 g, 66%) as a bright orange solid.

1. temperatureThe temperature of the oil-bath was raised to 120° C.
2. stirringthe heating and stirring
3. waitcontinued for an additional 120 min
4. temperatureThe reaction mixture was then cooled to 25° C.
5. concentrationconcentrated in vacuo to a volume of about 10 mL
6. customThe oily residue was partitioned with water (50 mL) and ethyl acetate (50 mL)
7. extractionThe aqueous phase was further extracted with ethyl acetate (2×50 mL)
8. extractioneach organic extract
9. washwas washed with a portion of a saturated aqueous sodium chloride solution (25 mL)
10. dry with materialThe combined organic extracts were dried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo to a dark oil
13. additionThe residue was treated with a solution of diethyl ether/hexanes (50 mL, 3:2)
14. customto produce an orange solid
15. filtrationThe solid was collected by filtration
16. washwashed with a mixture of diethyl ether/hexanes (25 mL, 1:1)

ORD record

ord-39580860cd804633b30f2e49e0955e3d

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07132425B2