Pyridine → 6-Chloro-2-isobutylamino-nicotinonitrile

HRID 1471607Notes

Reaction equation

HRID 1471607 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=O)=[C:4](OCC(C)C)[N:3]=1.[N:16]1[CH:21]=[CH:20][CH:19]=CC=1.O=P(Cl)(Cl)Cl.[OH-].[Na+].[C:29](#N)C>CCOC(C)=O>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]#[N:8])=[C:4]([NH:16][CH2:21][CH:20]([CH3:29])[CH3:19])[N:3]=1

Participants

7

Reactant 5

HCID 1049PyridineHCID 6342AcetonitrileHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 579689596-Chloro-2-isobutoxy-nicotinamide

Product 1

HCID 866364716-Chloro-2-isobutylamino-nicotinonitrileYield 91%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of 6-chloro-2-isobutoxy-nicotinamide (3, 2.39 g, 10.4 mmol) in acetonitrile (anhydrous, 150 mL) were added pyridine (6.75 mL, 83.5 mmol) and POCl3 (3.82 mL, 41.7 mmol). The reaction was heated at 55° C. for 3 hours. After cooling to room temperature, NaOH solution (10% aq.) was slowly added till pH 9. EtOAc (60 mL) was added and the layers separated. The aqueous layer was extracted with EtOAc (2×60 mL). The combined organic layer was dried over MgSO4, filtered, and concentrated in vacuo. Purification was accomplished by silica gel chromatography, eluting with 2%-30% EtOAc/hexanes gradient, to afford 2 g (91% yield) of the title product.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe layers separated
  3. extractionThe aqueous layer was extracted with EtOAc (2×60 mL)
  4. dry with materialThe combined organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification
  8. washeluting with 2%-30% EtOAc/hexanes gradient

Sources & evidence

ORD record
ord-d2d0ccb77398477f8d337e5f1c3d1009
Source dataset
uspto-grants-2015_04
Patent number
US09012431B2

Reaction notes

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