4-Methoxybenzylamine → 6-Ethylsulfanyl-5-fluoro-2-(4-methoxy-benzylamino)-nicotinic acid ethyl ester
Reaction equation
[CH2:1]([O:3][C:4](=[O:16])[C:5]1[CH:10]=[C:9]([F:11])[C:8]([S:12][CH2:13][CH3:14])=[N:7][C:6]=1Cl)[CH3:2].[CH3:17][O:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][NH2:24])=[CH:21][CH:20]=1>C(O)C>[CH2:1]([O:3][C:4](=[O:16])[C:5]1[CH:10]=[C:9]([F:11])[C:8]([S:12][CH2:13][CH3:14])=[N:7][C:6]=1[NH:24][CH2:23][C:22]1[CH:25]=[CH:26][C:19]([O:18][CH3:17])=[CH:20][CH:21]=1)[CH3:2]Participants
4
Procedure
A solution of 2-chloro-6-ethylsulfanyl-5-fluoro-nicotinic acid ethyl ester (66) (53 g, 201 mmol) in anhydrous ethanol was purged with argon and added p-methoxybenzylamine (52.5 mL, 402 mmol) at room temperature. The solution was refluxed overnight under argon. The solution was cooled and the solvent was evaporated under reduced pressure. The residue was taken in dichloromethane, sonicated briefly and undissolved solids were filtered off. The filtrate washed by water, dried over MgSO4 and concentrated. The crude product was purified by flash chromatography eluting with hexane:CH2Cl2 (1:1) to yield 47 g (64%) of 6-ethylsulfanyl-5-fluoro-2-(4-methoxy-benzylamino)-nicotinic acid ethyl ester (67) as a viscous oil which solidified to a white solids after keeping several days under vacuum at room temperature. Mp 59° C. 1H-NMR (DMSO-d6): δ 1.18 (t, J=7.2 Hz, 3H), 1.29 (t, J=7.2 Hz, 3H), 3.08 (q, J=7.2 Hz, 2H), 3.71 (s, 3H), 4.26 (q, J=7.2 Hz, 2H), 4.62 (d, J=5.6 Hz, 2H), 6.87 (m, 2H), 7.24 (m, 2H), 7.71 (d, J=10 Hz, 1H), 8.32 (m, 1H); EIMS m/z 365 (M+1).