Benzylamine → N-benzyl-2-chloro-6-methoxyisonicotinamide

To a solution of 2-chloro-6-methoxyisonicotinic acid (4.90 g, 26.00 mmol, prepared according to Okajima S., Yakugaku Zasshi, (1953), 73, 845-847) and 4-methylmorpholine (3.3 mL, 30.00 mmol) in tetrahydrofuran (100 mL) was added isobutyl chloroformate (3.8 mL, 28.00 mmol) at 0° C. The resulting solution was stirred at ambient temperature for 1 hour, followed by the addition of benzylamine (4.2 mL, 38.00 mmol). The reaction mixture was stirred at ambient temperature for 20 hours, diluted with ethyl acetate (100 mL), washed with water (30 mL) and brine (30 mL). The organic solution was dried over anhydrous sulphate, filtered and concentrated in vacuo. The residue was recrystallized from ethyl acetate and hexanes to give N-benzyl-2-chloro-6-methoxyisonicotinamide (6.20 g, 86%): 1H NMR (300 MHz, CDCl3) δ 7.37-7.27 (m, 5H), 7.18 (s, 1H), 6.94 (s, 1H), 6.43 (br s, 1H), 4.58 (d, J=5.7 Hz, 2H), 3.94 (s, 3H); MS (ES+) m/z 277.4 (M+1).

1. stirringThe reaction mixture was stirred at ambient temperature for 20 hours
2. washwashed with water (30 mL) and brine (30 mL)
3. dry with materialThe organic solution was dried over anhydrous sulphate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was recrystallized from ethyl acetate and hexanes

ORD record

ord-77f566a474354ebc8500cd2704a2d0f7

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09187426B2