Reaction equation
[C:1]([NH2:9])(=[S:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.[CH2:10]([O:12][C:13](=[O:22])[CH:14](Cl)[C:15](=O)[C:16]([F:19])([F:18])[F:17])[CH3:11].CCN(CC)CC>C(O)C>[CH2:10]([O:12][C:13]([C:14]1[S:8][C:1]([C:2]2[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=2)=[N:9][C:15]=1[C:16]([F:17])([F:18])[F:19])=[O:22])[CH3:11]Participants
Conditions
- Temperature
- 150 °C
Procedure
To a 20 mL microwave tube was added thionicotinamide (0.552 g, 4.0 mmol), ethanol (15 mL) and 2-chloro-4,4,4-trifluoro-3-oxo-butyric acid ethyl ester (1.75 g, 8 mmol). The tube was capped and heated in a microwave at 150° C. for 10 min. The reaction mixture was cooled to ambient temperature and Et3N (1.7 mL, 12 mmol) was added. The tube was capped and heated in a microwave at 130° C. for 1 min. After cooling to ambient temperature the solvent was evaporated and the crude reaction mixture was directly subjected to silica gel chromatography (0 to 100% ethyl acetate/hexanes) to give the desired product as an orange oil which subsequently solidified (0.885 g, 73%): IR (KBr) 2988, 1737, 1712 cm−1; 1H NMR (300 MHz, CDCl3) δ 9.21 (dd, J=2.5, 0.8 Hz, 1H), 8.77 (dd, J=5.0, 1.7 Hz, 1H), 8.33 (dt, J=8.0, 2.2 Hz, 1H), 7.47 (ddd, J=11.8, 4.7, 0.8 Hz, 1H), 4.45 (q, J=14.3, 7.1 Hz, 2H), 1.44 (t, J=7.1 Hz, 3H); ESIMS m/z 303 (M+1).
Workup
- customThe tube was capped
- temperatureThe reaction mixture was cooled to ambient temperature
- customThe tube was capped
- temperatureheated in a microwave at 130° C. for 1 min
- temperatureAfter cooling to ambient temperature the solvent
- customwas evaporated
- customthe crude reaction mixture
Sources & evidence
- ORD record
- ord-2a69de3e7e884e0f845b56aa6f7ea77b
- Source dataset
- uspto-grants-2014_10
- Patent number
- US08853246B2
Linked notes
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