Dimethylformamide → HCID 21959006, compound

Temperature

25 °C

A mixture of 5-methylpyrazine-2-carboxylic acid (2.76 g, 20 mmol) and oxalyl chloride (1.83 mL, 2.66 g, 21 mmol) in methylene chloride (40 mL) was treated with N,N-dimethylformamide (0.5 mL), and the mixture was stirred at 25° C. for 1 h. The mixture was filtered, and the filtrate was concentrated in vacuo to give an oily solid. The solid was dissolved in acetone (120 mL) at 0° C. and then sodium azide (1.03 g, 20 mmol) in water (50 mL) was added dropwise. After the addition was complete, stirring was continued at 0° C. for 30 min. The mixture was then poured into ice cold water (100 mL) and extracted with methylene chloride 3×100 mL). The combined organic extracts were washed with water 1×100 mL), a mixture of a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution (1:1, 1×100 mL), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated in vacuo to give 5-methyl-pyrazine-2-carbonyl azide (1.46 g, 45%) as a tan solid. The 5-methyl-pyrazine-2-carbonyl azide (500 mg, 3.07 mmol) was combined with benzyl alcohol (0.63 mL, 663 mg, 6.14 mmol) at 25° C. The mixture was then slowly heated on an oil bath to 90° C., upon which gas was violently evolved. The oil bath temperature was maintained until gas evolution ceased. The oil bath temperature was raised to 120° C. and stirring was continued for 10 min at that temperature. The mixture was cooled and triturated with diethyl ether/hexanes (1:4) to give (5-methylpyrazin-2-yl)-carbamic acid phenyl ester (438 mg, 58%) as a yellow solid. The (5-methylpyrazin-2-yl)-carbamic acid phenyl ester (500 mg, 2.2 mmol) and 10% palladium on carbon (212 mg) were mixed in ethanol (30 mL). The reaction vessel was flushed with hydrogen, and the mixture was stirred at 25° C. for 1 h under hydrogen (1 atm). The excess hydrogen was evacuated from the reaction vessel, and the mixture was filtered through a pad of celite. Concentration of the filtrate in vacuo gave 2-amino-5-methylpyrazine (183 mg , 76%) as a tan solid which was used without further purification.

1. filtrationThe mixture was filtered
2. concentrationthe filtrate was concentrated in vacuo
3. customto give an oily solid
4. additionAfter the addition
5. stirringstirring
6. waitwas continued at 0° C. for 30 min
7. extractionextracted with methylene chloride 3×100 mL)
8. washThe combined organic extracts were washed with water 1×100 mL),
9. additiona mixture of a saturated aqueous sodium bicarbonate solution
10. dry with materiala saturated aqueous sodium chloride solution (1:1, 1×100 mL), and dried over anhydrous sodium sulfate
11. filtrationThe mixture was filtered
12. concentrationconcentrated in vacuo

ORD record

ord-e15c08d9e2404c0abfa0cc90aec5b43c

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07259166B2