反应详情

N-(methyl(oxo){1-[6-(trifluoromethyl)-3-pyridinyl]ethyl}-λ6-sulfanylidene)thiourea (J) (100 mg, 0.321 mmol) and 5-bromo-6,7-dihydrobenzo[c][1,2,5]oxadiazol-4(5H)-one (76.6 mg, 0.353 mmol, 1.1 eq) were suspended in EtOH (1.6 mL). The reaction was stirred at room temperature for 2 h, and then heated to reflux for 1 h. The hot solution was filtered via a 0.45 μm nylon syringe filter and the filtrate was stored at −20° C. over night. 7-[(methyl(oxo){1-[6-(trifluoromethyl)-3-pyridinyl]ethyl}-λ6-sulfanylidene)amino]-4,5-dihydro[1,3]thiazolo[4,5-e][2,1,3]benzoxadiazole (65) was obtained in form of slightly yellow crystals (70 mg, 0.163 mmol, 51%) as a 1:1 mixture of diastereomers (racemate) that were isolated by filtration, washed with a small amount of cold ethanol, and dried in the high vacuum. 1H-NMR (DMSO-d6, 400 MHz): δ=1.87 (d, J=6.9 Hz, 1.5H, CHCH3, diastereomer 1); 1.89 (d, J=6.9 Hz, 1.5H, CHCH3, diastereomer 2); 3.06-3.27 (m, 4H, CH2—CH2, diastereomers 1, 2); 3.42 (s, 1.5H, S—CH3, diastereomer 1); 3.43 (s, 1.5H, S—CH3, diastereomer 2); 5.34 (q, J=6.9 Hz, 1H, CHCH3, diastereomers 1, 2); 7.96 (d, J=7.7 Hz, 0.5H, pyr-C3-H, diastereomer 1), 7.98 (d, J=7.8 Hz, 0.5H, pyr-C3-H, diastereomer 2); 8.21-8.26 (m, 1H, pyr-C4-H, diastereomers 1, 2); 8.85 (d, 0.5H 4J=1.6 Hz, pyr-C6-H, diastereomer 1); 8.86 (d, 0.5H, 4J=1.6 Hz, pyr-C6-H, diastereomer 2). 13C-NMR (DMSO-d6, 100 MHz): δ=13.3, 13.6 (CHCH3, two diastereomers); 17.9 (double peak, CH2, two diastereomers); 20.4 (double peak, CH2, two diastereomers); 36.4, 36.5 (S—CH3, two diastereomers); 60.8, 60.9 (CHCH3, two diastereomers); 119.4, 119.5 (pyr-C, two diastereomers); 120.3 (q, 2J (C—F)=271.5 Hz, CF3, two diastereomers), 131.6, 131.9; (pyr-C, two diastereomers); 132.0, 132.1 (Ar, two diastereomers), 132.4, 132.5 (Ar, two diastereomers); 138.0, 138.1 (pyr-C, two diastereomers); 145.0 (double peak, Ar, two diastereomers); 145.0, 145.1 (Ar, two diastereomers); 149.9 (double peak, pyr-C, two diastereomers); 151.2 (double peak, Ar, two diastereomers); 166.3, 166.6 (thiazole, two diastereomers). UPLC-MS (ESI+): mass calc'd for C16H15F3N5O2S2 (M+H+): 430.1. Found 430.1, UPLC-MS (ESI−) mass calc'd for C16H13F3N5O2S2 (M−H+): 428.1. Found 428.1.

1. temperatureheated
2. temperatureto reflux for 1 h
3. filtrationThe hot solution was filtered via a 0.45 μm nylon syringe
4. filtrationfilter
5. waitthe filtrate was stored at −20° C. over night