Water → 2-Cyano-5-fluoro-3-(2-pyridin-2-ylethylamino)pyridine

HRID 1877517Notes

Reaction equation

HRID 1877517 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][CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1.C(=O)([O-])[O-].[K+].[K+].O>CS(C)=O.C(OCC)(=O)C>[C:1]([C:3]1[C:8]([NH:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[CH:7][C:6]([F:10])=[CH:5][N:4]=1)#[N:2]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 759192-PyridineethanamineHCID 27832532-Cyano-3,5-difluoropyridine

Product 1

HCID 670168442-Cyano-5-fluoro-3-(2-pyridin-2-ylethylamino)pyridineYield 37.8%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
115 °C

Procedure

841 mg of 2-cyano-3,5-difluoropyridine, 880 mg of 2-(2-aminoethyl)pyridine and 1.658 g of potassium carbonate in 12.5 ml of dimethyl sulphoxide are introduced into a 20 ml microwave tube reactor. The mixture is then heated in a microwave for 1 and a half hours 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 ethyl acetate and cyclohexane (40/60 by volume), and the first eluted product being recovered, 549 mg of 2-cyano-5-fluoro-3-(2-pyridin-2-ylethylamino)pyridine are thus obtained in the form of a beige 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 ethyl acetate and cyclohexane (40/60 by volume)
  8. customthe first eluted product being recovered

Sources & evidence

ORD record
ord-785175c821a54b1e9c196bb17eb8d556
Source dataset
uspto-grants-2012_11
Patent number
US08309721B2

Reaction notes

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