Potassium Carbonate → Methyl 5-fluoro-2-(3-((4-fluoro-2-methylphenyl)amino)azetidin-1-yl)nicotinate

HRID 72450Notes

Reaction equation

HRID 72450 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]([F:12])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].C(=O)([O-])[O-].[K+].[K+].[F:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26][CH:27]2[CH2:30][NH:29][CH2:28]2)=[C:22]([CH3:31])[CH:21]=1>O1CCCC1>[F:12][C:9]1[CH:10]=[N:11][C:2]([N:29]2[CH2:30][CH:27]([NH:26][C:23]3[CH:24]=[CH:25][C:20]([F:19])=[CH:21][C:22]=3[CH3:31])[CH2:28]2)=[C:3]([CH:8]=1)[C:4]([O:6][CH3:7])=[O:5]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 24229209Methyl 2-chloro-5-fluoronicotinateHCID 65958632N-(4-fluoro-2-methylphenyl)azetidin-3-amine

Product 1

HCID 67958301Methyl 5-fluoro-2-(3-((4-fluoro-2-methylphenyl)amino)azetidin-1-yl)nicotinateYield 44.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of methyl 2-chloro-5-fluoronicotinate (D69) (199.85 mg, 1.054 mmol) and potassium carbonate (291 mg, 2.108 mmol) in tetrahydrofuran (2 ml) was stirred under N2 nitrogen 15 min at room temperature. N-(4-fluoro-2-methylphenyl)azetidin-3-amine (D55) (190 mg, 1.054 mmol) was added and the resulting mixture was stirred 1 day at room temperature. The residue obtained after solvent evaporation was purified by Biotage SNAP-Si column eluting with a mixture cyclohexane/ethyl acetate from 100/0 to 80/20. Collected fractions after solvent evaporation afforded the title compound (D90)(155 mg)

Workup

  1. stirringthe resulting mixture was stirred 1 day at room temperature
  2. customThe residue obtained
  3. customafter solvent evaporation
  4. customwas purified by Biotage SNAP-Si column
  5. washeluting with a mixture cyclohexane/ethyl acetate from 100/0 to 80/20
  6. customCollected fractions after solvent evaporation

Sources & evidence

ORD record
ord-978f35b8d72e424cbbcdf9cc7c60cb9d
Source dataset
uspto-grants-2014_09
Patent number
US08828987B2

Reaction notes

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