Hydrochloric Acid → HCID 10423223, compound

HRID 373872Notes

Reaction equation

HRID 373872 reaction equation
[F:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:3]=1[CH2:4][NH:5][C:6]1[CH:11]=[CH:10][N:9]=[CH:8][C:7]=1[N+:12]([O-])=O.[ClH:20]>O>[NH2:12][C:7]1[C:8]([Cl:20])=[N:9][CH:10]=[CH:11][C:6]=1[NH:5][CH2:4][C:3]1[C:2]([F:1])=[CH:18][CH:17]=[CH:16][C:15]=1[F:19]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 104229624-Pyridinamine, N-[(2,6-difluorophenyl)methyl]-3-nitro-

Product 1

HCID 10423223HCID 10423223, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A 3-neck 5-L flask, equipped with a thermometer, reflux condenser, nitrogen inlet and a mechanical stirrer was charged with 4-[(2,6-difluorobenzyl)amino]3-nitropyridine(146g, 0.55mol) and concentrated hydrochloric acid(1.4L, 16.8mol). The solution was heated on a steam bath to 90° C. and stannous chloride dihydrate(659g, 2.92mol) was added portionwise. After heating the suspension at 90° C. for 1.5 hours, the condenser was replaced with a distillation apparatus and approximately 1.5L of H2O removed by distillation at 100mm Hg. The remaining suspension was cooled in an ice bath and neutralized to pH 7 with concentrated ammonium hydroxide. The pasty solid was collected by filtration and dried overnight on a Buechner funnel. The still damp solid was transferred to a 12-L flask equipped with a mechanical stirrer and reflux condenser and charged with ethyl acetate. With rapid stirring, the suspension was heated at reflux for 3.5 hours on a steam bath, cooled slightly, filtered using positive nitrogen pressure, and the filtrate concentrated in vacuo. The resulting oily solid was slurried in ethyl ether, solids collected by filtration and dried overnight on a Buechner funnel to yield 123g (83.1%) of 3-amino-2-chloro-4-[(2,6-difluorobenzyl)amino]pyridine. TLC (silica gel, EtOAc/ether, 1:1) Rf =0.71; mp=221°-2230° C.; 1H NMR (DMSO-d6): 4.36(d,J=5.1 Hz, 2H, CH2), 4.84 (s, 2H, NH2), 6.06(t, J=5.1 Hz, 1H, NH), 6.54(d,J=5.4Hz, 1H, C-5H), 7.01-7.65 (m, 3H, C-3'H, C-4'H, C-5'H), 7.44 (d, J=5.3 Hx, 1H, C-6H).

Workup

  1. temperaturereflux condenser, nitrogen inlet and a mechanical stirrer
  2. temperatureAfter heating the suspension at 90° C. for 1.5 hours
  3. customremoved by distillation at 100mm Hg
  4. temperatureThe remaining suspension was cooled in an ice bath
  5. filtrationThe pasty solid was collected by filtration
  6. customdried overnight on a Buechner funnel
  7. customThe still damp solid was transferred to a 12-L flask
  8. customequipped with a mechanical stirrer
  9. temperaturereflux condenser
  10. additioncharged with ethyl acetate
  11. temperatureWith rapid stirring, the suspension was heated
  12. temperatureat reflux for 3.5 hours on a steam bath
  13. temperaturecooled slightly
  14. filtrationfiltered
  15. concentrationthe filtrate concentrated in vacuo
  16. filtrationsolids collected by filtration
  17. customdried overnight on a Buechner funnel

Sources & evidence

ORD record
ord-72a69b61fa5249379d5906a7bf85ec6e
Source dataset
uspto-grants-1992_11
Patent number
US05166209

Reaction notes

Loading…