5-Fluoro-4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile → 3-(Aminomethyl)-5-fluoro-4,6-dimethyl-2(1H)-pyridinone

HRID 1959313Notes

Reaction equation

HRID 1959313 reaction equation
[F:1][C:2]1[C:3]([CH3:12])=[C:4]([C:10]#[N:11])[C:5](=[O:9])[NH:6][C:7]=1[CH3:8]>N.CO>[NH2:11][CH2:10][C:4]1[C:5](=[O:9])[NH:6][C:7]([CH3:8])=[C:2]([F:1])[C:3]=1[CH3:12]

Participants

3

Reactant 1

HCID 671241755-Fluoro-4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile

Product 1

HCID 671242643-(Aminomethyl)-5-fluoro-4,6-dimethyl-2(1H)-pyridinoneYield 41%

Reagents, catalysts & solvents 1

HCID 21705897Ammonia methanolSolvent

Procedure

A solution of 0.05M 5-fluoro-4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (731 mg, 4.4 mmol) in 1.75M NH3/MeOH (87 ml) was passed through the H-Cube at 80° C. and 50 bar at a flow rate of 1 ml/min. The resulting solution was concentrated in-vacuo. The resulting solid was split into 2 batches and 350 mg of the crude product was purified by column chromatography (25 g SNAP cartridge, Isolera, 0-25% MeOH (containing 10% NH4OH):CH2Cl2) to give the title compound (307 mg, 20%) as an off white solid and a 1:1 mixture of product:starting material. LC-MS (ELS) 100%, 0.23 min (3.5 minute LC-MS method), m/z=170.9, 1H NMR (500 MHz, Chloroform-d) δ ppm 3.79 (s, 2H) 2.31 (d, J=2.84 Hz, 3H) 2.25 (d, J=2.05 Hz, 3H).

Workup

  1. customwas passed through the H-Cube at 80° C.
  2. concentrationThe resulting solution was concentrated in-vacuo
  3. customThe resulting solid was split into 2 batches and 350 mg of the crude product
  4. customwas purified by column chromatography (25 g SNAP cartridge, Isolera, 0-25% MeOH (containing 10% NH4OH):CH2Cl2)

Sources & evidence

ORD record
ord-c7f4d96d38cc4b4eb4d645961f0ecef7
Source dataset
uspto-grants-2013_04
Patent number
US08410088B2

Reaction notes

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