Pyridine → 2-tert-Butylamino-6-chloro-nicotinonitrile
Reaction equation
[C:1]([NH:5][C:6]1[N:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:7]=1[C:8]([NH2:10])=O)([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.O=P(Cl)(Cl)Cl.[OH-].[Na+]>C(#N)C>[C:1]([NH:5][C:6]1[N:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:7]=1[C:8]#[N:10])([CH3:4])([CH3:2])[CH3:3]Participants
6
Conditions
- Temperature
- 55 °C
Procedure
To a solution of 2-tert-butylamino-6-chloro-nicotinamide (3, 850 mg, 3.73 mmol) in acetonitrile (anhydrous, 40 mL) were added pyridine (2.42 mL, 29.9 mmol) and POCl3 (1.37 mL, 14.9 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. The solution was extracted with EtOAc (3×50 mL). The combined organic layer was dried over MgSO4, filtered, and concentrated in vacuo. Purification was accomplished by Biotage silica gel chromatography, eluting with 2%-30% EtOAc/hexanes gradient, to afford 630 mg (80% yield) of the title product.
Workup
- temperatureAfter cooling to room temperature
- extractionThe solution was extracted with EtOAc (3×50 mL)
- dry with materialThe combined organic layer was dried over MgSO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customPurification
- washeluting with 2%-30% EtOAc/hexanes gradient
Sources & evidence
- ORD record
- ord-a3a08e43237e4ec5b874dabd30372a77
- Source dataset
- uspto-grants-2016_08
- Patent number
- US09416146B2
Reaction notes
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