Triethylamine → (Azetidin-1-yl)(5-chloropyrazin-2-yl)methanone

Oxalyl chloride (1.55 mL, 17.5 mmol), followed by DMF (2 drops), was added to a mixture of 5-chloropyrazine-2-carboxylic acid (CAS no. 36070-80-1, Intermediate 33) (2.31 g, 14.6 mmol) in DCM (40 mL). The reaction was stirred at RT for 2 hours after which time the volatiles were removed under reduced pressure. The residue was taken up DCM (40 mL) and azetidine (1.08 mL, 16.03 mmol) and triethylamine (4.46 mL, 32.06 mmol) added. The mixture was stirred at RT for 72 hours. The volatiles were removed under reduced pressure and ethyl acetate (100 mL) added to the residue. The organics were washed with water (100 mL), citric acid (50 mL), saturated sodium bicarbonate solution (50 mL) and brine (50 mL), dried (MgSO4), filtered and the solvent removed under reduced pressure. The residue was purified by flash chromatography, eluting with a gradient of 50-100% ethyl acetate in isohexane, to afford the product (2.38 g, 82%). 1HNMR δ (400 MHZ, CDCl3): 2.35-2.42 (2H, m), 4.26 (2H, t), 4.67 (2H, t), 8.52 (1H, d), 9.09 (1H, d); m/z 198 (M+H)+.

1. customwere removed under reduced pressure
2. additionadded
3. stirringThe mixture was stirred at RT for 72 hours
4. customThe volatiles were removed under reduced pressure and ethyl acetate (100 mL)
5. additionadded to the residue
6. washThe organics were washed with water (100 mL), citric acid (50 mL), saturated sodium bicarbonate solution (50 mL) and brine (50 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. customthe solvent removed under reduced pressure
10. customThe residue was purified by flash chromatography
11. washeluting with a gradient of 50-100% ethyl acetate in isohexane

ORD record

ord-922187e9d99d4b4b9e514ffc12b3b231

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07902200B2