2-Chloro-3-pyridylamine → HCID 54263873, compound

HRID 1376814Notes

Reaction equation

HRID 1376814 reaction equation
[NH2:1][C:2]1[C:3]([Cl:8])=[N:4][CH:5]=[CH:6][CH:7]=1.[CH3:9][O:10][C:11]1[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][C:12]=1[CH:13]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C>[Cl:8][C:3]1[C:2]([NH:1][CH2:13][C:12]2[CH:15]=[C:16]([O:19][C:20]([F:21])([F:22])[F:23])[CH:17]=[CH:18][C:11]=2[O:10][CH3:9])=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

5

Reactant 3

HCID 805282-Chloro-3-pyridylamineHCID 27833642-Methoxy-5-(trifluoromethoxy)benzaldehydeHCID 5049666Sodium triacetoxyborohydride2×

Product 1

HCID 54263873HCID 54263873, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
25 °C

Procedure

To a 75 mL 3-necked round bottom flask fitted with mechanical stirrer, thermometer, addition funnel, and nitrogen inlet, were charged 29 mL acetic acid and 1.45 grams (11.3 mmoles) 3-amino-2-chloropyridine. The mixture was agitated for 5 minutes at 25° C. for dissolution. To the resulting solution was added 3.10 grams (14.1 mmoles/1.25 equivalents) of 2-methoxy-5-trifluoromethoxy benzaldehyde. Sodium triacetoxyborohydride, (4.79 grams, 22.6 mmoles, 2.0 equivalents) was added in portions while maintaining the temperature below 25° C. The reaction mixture was stirred 22 hours at 25° C. before adding another 0.5 grams of sodium triacetoxyborohydride. After stirring an additional 1 hour and 15 minutes, the reaction mixture was vacuum concentrated to 12.5 mL and partitioned between 26 mL each of methylene chloride and water. The pH was adjusted to 9.5 with 25% sodium hydroxide solution while maintaining a temperature of 25°-30° C. with cooling. The layers were separated, and the aqueous layer was washed with 14.5 mL methylene chloride. The methylene chloride layers were combined and dried with magnesium sulfate. The magnesium sulfate was removed by filtration, and the methylene chloride filtrate was evaporated and displaced with ethyl acetate, which resulted in a yellow oil (3.49 gms/92.8% weight yield). The structure of the product was established by high resolution NMR and GC/MS. 1H NMR (CDCl3) 7.70 (dd, 1H), 7.09 (bs, 1H), 7.02 (m, 2H), 6.85 (m, 2H), 4.95 (t, 1H), 4.36 (d, 2H), 3.88 (s, 3H).

Workup

  1. customTo a 75 mL 3-necked round bottom flask fitted with mechanical stirrer
  2. additionthermometer, addition funnel, and nitrogen inlet
  3. temperaturewhile maintaining the temperature below 25° C
  4. stirringThe reaction mixture was stirred 22 hours at 25° C.
  5. stirringAfter stirring an additional 1 hour and 15 minutes
  6. concentrationconcentrated to 12.5 mL
  7. custompartitioned between 26 mL each of methylene chloride and water
  8. temperaturewhile maintaining a temperature of 25°-30° C.
  9. temperaturewith cooling
  10. customThe layers were separated
  11. washthe aqueous layer was washed with 14.5 mL methylene chloride
  12. dry with materialdried with magnesium sulfate
  13. customThe magnesium sulfate was removed by filtration
  14. customthe methylene chloride filtrate was evaporated
  15. customresulted in a yellow oil (3.49 gms/92.8% weight yield)

Sources & evidence

ORD record
ord-956563b737234ce68ec57ce0586574ca
Source dataset
uspto-grants-1997_09
Patent number
US05663349

Reaction notes

Loading…