Oxalyl chloride → 5-bromo-N-(cyclopropylmethyl)nicotinamide

To a solution of 5-bromonicotinic acid (XVI) (1.01 g, 5 mmol) in dry DCM (10 mL) under nitrogen was added oxalyl chloride (0.654 mL, 7.5 mmol) followed by dry DMF (0.1 mL) The solution was stirred at r.t. for 30 min. The solvent was evaporated under vacuum before adding dry pyridine (10 mL) followed by cyclopropylmethanamine (0.39 mL, 4.5 mmol). The solution was stirred at r.t. under nitrogen for 2 h. The solution was poured into ice water, basified with sat. aq. NaHCO3 and extracted with DCM. The combined organic phases were dried over MgSO4, concentrated and dried under vacuum to yield 5-bromo-N-(cyclopropylmethyl)nicotinamide (XVII) as an off-white solid (0.82 g, 3.2 mmol, 71% yield). 1H NMR (DMSO-d6) δ ppm −0.07-0.07 (m, 2H), 0.15-0.29 (m, 2H), 0.68-0.88 (m, 1H), 2.93 (t, J=6.22 Hz, 2H), 8.20 (t, J=1.88 Hz, 1H), 8.62 (d, J=1.70 Hz, 2H), 8.75 (s, 1H); ESIMS found C10H11BrN2O m/z 254, 256 (M+, M+2).

1. customThe solvent was evaporated under vacuum
2. additionbefore adding dry pyridine (10 mL)
3. stirringThe solution was stirred at r.t. under nitrogen for 2 h
4. extractionextracted with DCM
5. dry with materialThe combined organic phases were dried over MgSO4
6. concentrationconcentrated
7. customdried under vacuum

ORD record

ord-e8e6707813274da291650f34cbf3bc81

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08604052B2