Sodium Methoxide → 1H,2H,3H,4H,5H-pyrido[2,3-e][1,4]diazepin-3-one

Raney nickel (3 g) was added to anhydrous methanol (50 mL) under argon and washed with anhydrous methanol (4×50 mL) (3-Cyanopyridin-2-ylamino)-acetic acid ethyl ester (3.35 g, 16.3 mmol) was dissolved in methanol (50 mL) and added to the Raney nickel slurry. The reaction vessel was purged with argon for 10 min. Sodium methoxide solution (16.3 mmol, 3.75 mL) was added and the argon purge was repeated (5 min). The reaction flask was charged with H2 and stirred at room temperature for 48 h. Dilute HCl (16.3 mL of a 1 M solution) was added and the flask was purged with argon for 30 min. The slurry was filtered through celite and the filter cake was washed with 1:1 methanol/water. The filtrate was concentrated and extracted with ethyl acetate (4×100 mL), dried over MgSO4 and concentrated to afford the title compound as a beige solid (850 mg, 30%). 1H NMR (300 MHz, DMSO-d6) δ 8.07 (t, J=5.2 Hz, 1H), 7.82 (dd, J=4.9, 1.5 Hz, 1H), 7.21 (dd, J=7.1, 1.6 Hz, 1H), 6.69 (t, J=5.0 Hz, 1H), 6.43 (dd, J=7.2, 5.0 Hz, 1H), 4.24 (d, J=5.9 Hz, 2H), 3.91 (d, J=5.1 Hz, 2H).

1. customThe reaction vessel was purged with argon for 10 min
2. customthe argon purge
3. custom(5 min)
4. additionThe reaction flask was charged with H2
5. additionDilute HCl (16.3 mL of a 1 M solution) was added
6. customthe flask was purged with argon for 30 min
7. filtrationThe slurry was filtered through celite
8. washthe filter cake was washed with 1:1 methanol/water
9. concentrationThe filtrate was concentrated
10. extractionextracted with ethyl acetate (4×100 mL)
11. dry with materialdried over MgSO4
12. concentrationconcentrated

ORD-Eintrag

ord-2e0689d7d35d4cc8a5f259a015cbe178

Quelldatensatz

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08450307B2