4-Cyanopiperidine → 1-(3-(4-(Pyridin-2-ylamino)-phenoxy)pyrazin-2-yl)piperidine-4-carbonitrile

HRID 473617Notes

Reaction equation

HRID 473617 reaction equation
Cl[C:2]1[C:3]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][N:7]=1.[NH:22]1[CH2:27][CH2:26][CH:25]([C:28]#[N:29])[CH2:24][CH2:23]1>CS(C)=O.O>[N:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[NH:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][C:3]2[C:2]([N:22]3[CH2:27][CH2:26][CH:25]([C:28]#[N:29])[CH2:24][CH2:23]3)=[N:7][CH:6]=[CH:5][N:4]=2)=[CH:10][CH:11]=1

Participants

5

Reactant 2

HCID 1382234-CyanopiperidineHCID 53485989N-(4-(3-chloropyrazin-2-yloxy)phenyl)pyridin-2-amine

Product 1

HCID 468320691-(3-(4-(Pyridin-2-ylamino)-phenoxy)pyrazin-2-yl)piperidine-4-carbonitrile

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

In a 50 mL round-bottomed flask was placed N-(4-(3-chloropyrazin-2-yloxy)-phenyl)pyridin-2-amine (0.2376 g, 0.7954 mmol) in DMSO. Piperidine-4-carbonitrile (0.4363 g, 3.977 mmol) was added and the temperature was brought to 80° C. to stir overnight. The reaction mixture was diluted with water (10 mL) and extracted with DCM (3×10 mL). The organic extract was washed with water (3×10 mL), satd sodium chloride solution (3×10 mL), dried with magnesium sulfate, filtered, and concentrated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage™ pre-packed silica gel column (25M), eluting with a gradient of 1% to 5% methanol in DCM, to provide 1-(3-(4-(pyridin-2-ylamino)-phenoxy)pyrazin-2-yl)piperidine-4-carbonitrile. MS (ESI, pos. ion) m/z: 373.1 (M+1). IC50 (uM) 0.006048.

Workup

  1. customIn a 50 mL round-bottomed flask was placed
  2. customwas brought to 80° C.
  3. extractionextracted with DCM (3×10 mL)
  4. extractionThe organic extract
  5. washwas washed with water (3×10 mL), satd sodium chloride solution (3×10 mL)
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customchromatographed through a Biotage™ pre-packed silica gel column (25M)
  10. washeluting with a gradient of 1% to 5% methanol in DCM

Sources & evidence

ORD record
ord-6d0cad921e7548978e3a4e442ff5c158
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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