6-Chloronicotinic acid → 5-(Azetidin-1-ylcarbonyl)-2-chloropyridine

HRID 909527Notes

Reaction equation

HRID 909527 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.Cl.[NH:12]1[CH2:15][CH2:14][CH2:13]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>ClCCl>[N:12]1([C:6]([C:5]2[CH:9]=[CH:10][C:2]([Cl:1])=[N:3][CH:4]=2)=[O:8])[CH2:15][CH2:14][CH2:13]1

Participants

6

Reactant 4

HCID 792226-Chloronicotinic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12308726Azetidine hydrochloride

Product 1

HCID 536296155-(Azetidin-1-ylcarbonyl)-2-chloropyridineYield 105.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Commercially available 6-chloronicotinic acid (160 mg, 1.01 mmol) was dissolved in dichloromethane (5 mL), and azetidine hydrochloride (130 mg, 1.39 mmol), HATU (420 mg, 1.10 mmol) and N,N-diisopropylethylamine (0.50 mL, 2.87 mmol) were added, followed by stirring at room temperature overnight under nitrogen atmosphere. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=40%-50%) to afford the desired compound (210 mg, yield ˜100%) as a colorless liquid.

Workup

  1. distillationThe solvent was distilled off under reduced pressure
  2. customthe resulting residue was purified
  3. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=40%-50%)

Sources & evidence

ORD record
ord-752f21d0432040e78e54dcb8e8ee4a3c
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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