Reaction equation
C(O[CH:4](OCC)[CH2:5][NH2:6])C.C[O-].[Na+].[N:13]1[CH:18]=[CH:17][N:16]=[CH:15][C:14]=1[C:19]#[N:20].C(O)(=O)C.Cl>CO>[NH:20]1[CH:4]=[CH:5][N:6]=[C:19]1[C:14]1[CH:15]=[N:16][CH:17]=[CH:18][N:13]=1Participants
Procedure
2,2-Diethoxyethanamine (3 g, 2.25 mmol) was dissolved in dry methanol (20 mL). To this was added sodium methoxide (1.22 g, 22.5 mmol, as a 25% solution in methanol). After stirring for 25 minutes at room temperature, pyrazine-2-carbonitrile (2.37 g, 22.5 mmol) and acetic acid (1.35 g, 22.5 mmol) were added and the subsequent solution was stirred at 50° C. for 1 hour. MeOH (40 mL) and 6N HCl (12 mL) were added and the reaction was stirred at reflux overnight. The reaction mixture was cooled to room temperature and partitioned between 1:1 Et2O and water (60 mL) and the layers were separated. The aqueous layer was basified to pH 9/10 and extracted with 10% MeOH in DCM. The combined organic extracts were dried (MgSO4), filtered and concentrated to give the desired compound (1.49 g yellow solid). 1H NMR (400 MHz, MeOH-d4) δ ppm: 7.67 (s, 1 H), 7.09 (d, J=1.8 Hz, 1 H), 6.99 (d, J=2.5 Hz, 1 H), 5.72 (s, 2 H)
Workup
- stirringthe subsequent solution was stirred at 50° C. for 1 hour
- stirringthe reaction was stirred
- temperatureat reflux overnight
- temperatureThe reaction mixture was cooled to room temperature
- custompartitioned between 1:1 Et2O and water (60 mL)
- customthe layers were separated
- extractionextracted with 10% MeOH in DCM
- dry with materialThe combined organic extracts were dried (MgSO4)
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-a496798308bf4c97828274c41e015864
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08822455B2
Linked notes
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