Triethylamine → 2-Cyano-5-fluoro-3-(tetrahydropyran-4-yl)aminopyridine

HRID 1877502Notes

Reaction equation

HRID 1877502 reaction equation
[C:1]([C:3]1[C:8](F)=[CH:7][C:6]([F:10])=[CH:5][N:4]=1)#[N:2].Cl.[NH2:12][CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.C(=O)([O-])[O-].[K+].[K+].C(N(CC)CC)C>CS(C)=O.C(OCC)(=O)C.O>[C:1]([C:3]1[C:8]([NH:12][CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:7][C:6]([F:10])=[CH:5][N:4]=1)#[N:2]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 27832532-Cyano-3,5-difluoropyridineHCID 441186934-Aminotetrahydropyran hydrochloride

Product 1

HCID 670167052-Cyano-5-fluoro-3-(tetrahydropyran-4-yl)aminopyridineYield 25.3%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
115 °C

Procedure

200 mg of 2-cyano-3,5-difluoropyridine, 236 mg of 4-aminotetrahydropyran hydrochloride, 395 mg of potassium carbonate and 173.4 mg of triethylamine in 3 ml of dimethyl sulphoxide are introduced into a 5 ml microwave tube reactor. The mixture is then heated in a microwave for 1 hour at 115° C. The reaction medium is run into 50 ml of water and 50 ml of ethyl acetate. The aqueous phase is re-extracted twice with 25 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 25 g of silica gel, elution being carried out with mixtures of ethyl acetate and heptane (40/60 then 60/40 by volume), and the first eluted product being recovered, 80 mg of 2-cyano-5-fluoro-3-(tetrahydropyran-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 25 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 25 g of silica gel, elution
  7. custom60/40 by volume), and the first eluted product being recovered

Sources & evidence

ORD record
ord-8beba0a0506647ada78e1492031e6961
Source dataset
uspto-grants-2012_11
Patent number
US08309721B2

Reaction notes

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