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. washwashed with anhydrous methanol (4×50 mL)
2. customThe reaction vessel was purged with argon for 10 min
3. customthe argon purge
4. custom(5 min)
5. additionThe reaction flask was charged with H2
6. additionDilute HCl (16.3 mL of a 1 M solution) was added
7. customthe flask was purged with argon for 30 min
8. filtrationThe slurry was filtered through celite
9. washthe filter cake was washed with 1:1 methanol/water
10. concentrationThe filtrate was concentrated
11. extractionextracted with ethyl acetate (4×100 mL)
12. dry with materialdried over MgSO4
13. concentrationconcentrated

ORD-Eintrag

ord-784058d8310b4f318990f004fb563744

Quelldatensatz

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07879872B2