Hydrochloric Acid → HCID 10399928, compound

HRID 2255425Notes

Reaction equation

HRID 2255425 reaction equation
[F:1][C:2]1[CH:18]=[CH:17][CH:16]=[CH:15][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.CO.[ClH:21]>C(OCC)(=O)C>[NH2:12][C:7]1[C:8]([Cl:21])=[N:9][CH:10]=[CH:11][C:6]=1[NH:5][CH2:4][C:3]1[CH:15]=[CH:16][CH:17]=[CH:18][C:2]=1[F:1]

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 887MethanolHCID 10332195HCID 10332195, compound

Product 1

HCID 10399928HCID 10399928, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mechanically stirred solution of 4-[(2-fluorobenzyl)amino]-3-nitropyridine (12.31 g, 49.8 mmol) in concentrated hydrochloric acid (118 ml) was heated to 90° under a nitrogen atm. Stannous chloride dihydrate (55.56 g, 246 mmol) was added in small portions over a 5 min period (the oil bath was removed until the reaction subsided). After an additional 30 min at 90°, the reaction mixture was cooled, diluted with water (200 ml) and spin evaporated in vacuo. The residue was diluted with water (200 ml) and cooled in an ice-bath, while concentrated ammonium hydroxide was added to adjust the pH to 7-8. The solids were collected and allowed to air dry overnight. The solid was treated with ethyl acetate and filtered (12×200 ml), the combined extracts were washed with water, dried (sodium sulphate) and spin evaporated in vacuo. The residue was combined with the product from a separate reaction (12 g, 48.5 mmoles) and dissolved in ethyl acetate. This solution was added to Silica Gel 60 and spin evaporated in vacuo. The residual solids were introduced to a column (5 cm×30 cm) of Silica Gel 60 wetted with ethyl acetate. The column was eluted with ethyl acetate using flash chromatography. The appropriate fractions were combined and spin evaporated in vacuo to give 20.8 g (84%) of 3-amino-2-chloro-4-[2-fluorobenzyl)amino]pyridine as a white solid, mp.=185°-187°; UV (0.1M hydrochloric acid+5% methanol), λmax 233 nm (ξ17900), 302 nm (ξ14900); (pH 7.0 buffer+5% methanol), λmax 262 nm (ξ11200), (0.1N sodium hydroxide+5% methanol), λmax 262 nm (ξ10700), 1H nmr (DMSO-d6): δ7.36-7.15 (complex m, 5H,Ar+pyridine H-6), 6.35-6.30 (d,1H,pyridine H-5), 6.27-6.33 (overlapping,1H,NH). 4.84 (2,2H,NH2), 4.41 (d,2H,J=5 Hz, CH2Ar).

Workup

  1. customwas removed until the reaction
  2. temperaturethe reaction mixture was cooled
  3. additiondiluted with water (200 ml)
  4. customspin evaporated in vacuo
  5. additionThe residue was diluted with water (200 ml)
  6. temperaturecooled in an ice-bath, while concentrated ammonium hydroxide
  7. additionwas added
  8. customThe solids were collected
  9. customto air dry overnight
  10. additionThe solid was treated with ethyl acetate
  11. filtrationfiltered (12×200 ml)
  12. washthe combined extracts were washed with water
  13. dry with materialdried (sodium sulphate)
  14. customspin evaporated in vacuo
  15. customThe residue was combined with the product from a separate reaction (12 g, 48.5 mmoles)
  16. additionThis solution was added to Silica Gel 60
  17. customspin evaporated in vacuo
  18. additionThe residual solids were introduced to a column (5 cm×30 cm) of Silica Gel 60
  19. washThe column was eluted with ethyl acetate using flash chromatography
  20. customspin evaporated in vacuo
  21. customto give 20.8 g (84%) of 3-amino-2-chloro-4-[2-fluorobenzyl)amino]pyridine as a white solid, mp.=185°-187°

Sources & evidence

ORD record
ord-50ab3f6fdbe846caaddd4b94f2cd0dd0
Source dataset
uspto-grants-1993_08
Patent number
US05240937

Reaction notes

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