Bromine → 7-Bromo-3,3-dimethyl-2,3-dihydro-1H-pyrido[2,3-e][1,4]diazepine
Reaction equation
[CH3:1][C:2]1([CH3:13])[CH2:8][NH:7][C:6]2[N:9]=[CH:10][CH:11]=[CH:12][C:5]=2[CH2:4][NH:3]1.[Br:14]Br>CN(C=O)C>[Br:14][C:11]1[CH:10]=[N:9][C:6]2[NH:7][CH2:8][C:2]([CH3:13])([CH3:1])[N:3]=[CH:4][C:5]=2[CH:12]=1Participants
4
Procedure
A solution of 3,3-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepine (0.43 g, 1.8 mmol) in DMF (20 mL) was cooled in an ice bath and treated drop-wise with Br2 (0.19 mL, 3.7 mmol). After stirring in the ice bath for 2.5 h, the reaction was quenched with H2O (25 mL) and NaHCO3 (50 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were washed with H2O (2×50 mL) and brine (50 mL), dried over Na2SO4, filtered and concentrated to an orange oil. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 98:2 to 96:4) gave the title compound (0.26 g, 54%) as a yellow solid: 1H NMR (300 MHz, DMSO-d6) δ 8.15 (d, J=2.3 Hz, 1H), 8.03 (s, 1H), 7.73 (d, J=2.3 Hz, 1H), 5.93 (br s, 1H), 3.09 (d, J=4.9 Hz, 2H), 1.30 (s, 6H); MS (ESI) m/e 254 (M+H)+.