4-Methoxybenzylamine → 6-Ethylsulfanyl-5-fluoro-2-(4-methoxy-benzylamino)-nicotinic acid ethyl ester

HRID 901247Notes

Reaction equation

HRID 901247 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

Reactant 2

HCID 754524-MethoxybenzylamineHCID 596996322-Chloro-6-ethylsulfanyl-5-fluoro-nicotinic acid ethyl ester

Product 1

HCID 596996366-Ethylsulfanyl-5-fluoro-2-(4-methoxy-benzylamino)-nicotinic acid ethyl esterYield 64.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

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).

Workup

  1. temperatureThe solution was refluxed overnight under argon
  2. temperatureThe solution was cooled
  3. customthe solvent was evaporated under reduced pressure
  4. customsonicated briefly
  5. filtrationundissolved solids were filtered off
  6. washThe filtrate washed by water
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe crude product was purified by flash chromatography
  10. washeluting with hexane:CH2Cl2 (1:1)

Sources & evidence

ORD record
ord-5ee9c720ea32457193a9df97d3380c44
Source dataset
uspto-grants-2008_04
Patent number
US07361760B2

Reaction notes

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