Trifluoroacetic acid → 5-fluoro-4-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)pyridin-3-amine

HRID 524953Notes

Reaction equation

HRID 524953 reaction equation
C(O)(C(F)(F)F)=O.[F:8][C:9]1[C:10]([C:23]2[CH2:24][CH2:25][N:26]([CH3:29])[CH2:27][CH:28]=2)=[C:11]([NH:15]C(=O)OC(C)(C)C)[CH:12]=[N:13][CH:14]=1>C(Cl)Cl>[F:8][C:9]1[C:10]([C:23]2[CH2:24][CH2:25][N:26]([CH3:29])[CH2:27][CH:28]=2)=[C:11]([NH2:15])[CH:12]=[N:13][CH:14]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86721008tert-butyl N-[5-fluoro-4-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-3-pyridyl]carbamate

Product 1

HCID 867210095-fluoro-4-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)pyridin-3-amineYield 19%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (2 mL, 25.96 mmol) was added to a stirred solution of tert-butyl N-[5-fluoro-4-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-3-pyridyl]carbamate (483 mg, 1.571 mmol) in DCM (10 mL) and the reaction stirred at ambient temperature for 6 hours. The solvent was removed in vacuo and the residue azeotroped with DCM (×2) and ether (×2). The residue was passed through a 10 g SCX-2 cartridge and washed with MeOH/DCM mixtures. The product was eluted by washing the cartridge with 2M NH3 in MeOH/DCM mixtures and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion, 40 g column, eluting with 0 to 10% MeOH/DCM+1% NH4OH, loaded in DCM) to give 5-fluoro-1′-methyl-1′,2′,3′,6′-tetrahydro-[4,4′-bipyridin]-3-amine as an off-white solid (61 mg, 19% Yield over 2 steps). MS (ES+) 208.1.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue azeotroped with DCM (×2) and ether (×2)
  3. washwashed with MeOH/DCM
  4. washThe product was eluted
  5. washby washing the cartridge with 2M NH3 in MeOH/DCM mixtures
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (ISCO Companion, 40 g column, eluting with 0 to 10% MeOH/DCM+1% NH4OH, loaded in DCM)

Sources & evidence

ORD record
ord-181ebfa6eaf24202a7eabce59c12212d
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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