Water → 2-Cyano-5-fluoro-3-(1,2,2,6,6-pentamethylpiperidin-4-yl)aminopyridine

HRID 1877507Notes

Reaction equation

HRID 1877507 reaction equation
[C:1]([C:3]1[C:8](F)=[CH:7][C:6]([F:10])=[CH:5][N:4]=1)#[N:2].[NH2:11][CH:12]1[CH2:17][C:16]([CH3:19])([CH3:18])[N:15]([CH3:20])[C:14]([CH3:22])([CH3:21])[CH2:13]1.O.C(OCC)(=O)C>CS(C)=O.C(=O)([O-])[O-].[K+].[K+]>[C:1]([C:3]1[C:8]([NH:11][CH:12]2[CH2:13][C:14]([CH3:21])([CH3:22])[N:15]([CH3:20])[C:16]([CH3:19])([CH3:18])[CH2:17]2)=[CH:7][C:6]([F:10])=[CH:5][N:4]=1)#[N:2]

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 6937924-Amino-1,2,2,6,6-pentamethylpiperidineHCID 27832532-Cyano-3,5-difluoropyridine

Product 1

HCID 583383532-Cyano-5-fluoro-3-(1,2,2,6,6-pentamethylpiperidin-4-yl)aminopyridineYield 20.5%

Reagents, catalysts & solvents 2

HCID 11430Potassium CarbonateCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
115 °C

Procedure

682 mg of 2-cyano-3,5-difluoropyridine, 995 mg of 4-amino-1,2,2,6,6-pentamethylpiperidine and 1.346 mg of potassium carbonate in 10 ml of dimethyl sulphoxide are introduced into a 20 ml microwave tube reactor. The mixture is then heated in the microwave for 1 hour at 115° C. The reaction medium is run into 100 ml of water and 100 ml of ethyl acetate. The aqueous phase is re-extracted twice with 50 ml of ethyl acetate. The combined organic phases are washed with water and then with a saturated aqueous solution of sodium chloride, dried over sodium sulphate and concentrated under reduced pressure. After purification by flash chromatography on 70 g of silica gel, elution being carried out with a mixture of dichloromethane, methanol and 4N aqueous ammonia (99/1/0.8 by volume), and the first eluted product being recovered, 290 mg of 2-cyano-5-fluoro-3-(1,2,2,6,6-pentamethylpiperidin-4-yl)aminopyridine are thus obtained in the form of an ecru powder, the characteristics of which are the following:

Workup

  1. extractionThe aqueous phase is re-extracted twice with 50 ml of ethyl acetate
  2. washThe combined organic phases are washed with water
  3. dry with materialwith a saturated aqueous solution of sodium chloride, dried over sodium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customAfter purification by flash chromatography
  6. washon 70 g of silica gel, elution
  7. additionbeing carried out with a mixture of dichloromethane, methanol and 4N aqueous ammonia (99/1/0.8 by volume)
  8. customthe first eluted product being recovered

Sources & evidence

ORD record
ord-ebbd255367b446169d7e52e2837024fa
Source dataset
uspto-grants-2012_11
Patent number
US08309721B2

Reaction notes

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