Hydrochloric Acid → 6-(4-Aminopiperidin-1-yl)pyridine-3-carbonitrile

HRID 874953Notes

Reaction equation

HRID 874953 reaction equation
Cl.[C:2]([C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([NH:16]C(=O)C)[CH2:12][CH2:11]2)=[N:8][CH:9]=1)#[N:3].[OH-].[Na+]>>[NH2:16][CH:13]1[CH2:14][CH2:15][N:10]([C:7]2[CH:6]=[CH:5][C:4]([C:2]#[N:3])=[CH:9][N:8]=2)[CH2:11][CH2:12]1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 49431041HCID 49431041, compound

Product 1

HCID 187686716-(4-Aminopiperidin-1-yl)pyridine-3-carbonitrileYield 85.1%

Conditions

Temperature
100 °C

Procedure

2N HCl (3 mL) was added to N-(1-(5-cyanopyridin-2-yl)piperidin-4-yl)acetamide (300 mg, 1.22 mmol) and the reaction mixture was stirred at 100° C. for 5 h. The reaction mixture was cooled to room temperature and the pH of the aqueous layer was adjusted to 8-9 using 10% NaOH solution. The product was extracted with CH2Cl2 and the combined extracts were washed with water and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford 6-(4-aminopiperidin-1-yl)nicotinonitrile (210 mg, crude), which was carried through without further purification. 1H NMR (300 MHz, DMSO-d6) δ 8.43 (d, J=2.3 Hz, 1H), 7.79-7.75 (dd, J=9.1 Hz, 2.3 Hz, 1H), 6.90 (d, J=9.2 Hz, 1H), 4.28-4.23 (m, 2H), 3.07-2.98 (m, 2H), 2.87-2.78 (m, 1H), 1.75-1.71 (m, 2H), 1.19-1.07 (m, 2H). MS (ESI) m/z: Calculated for C11H14N4: 202.12. found: 203.2 (M+H)+

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe product was extracted with CH2Cl2
  3. washthe combined extracts were washed with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2f1c042f61e9421b90c523c482428d6e
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

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