2-Phenylpropanal → 5-{1-[(5-Benzyl-1,3-thiazol-2-yl)(methyl)sulfonimidoyl]ethyl}-2-(trifluoromethyl)pyridine

Preparation of 2-bromo-3-phenylpropanal: dibromobarbituric acid (1.43 g, 5 mmol) was dissolved in diethylether (40 mL) and phenylpropionaldehyde (1.34 g, 1.33 mL, 10 mmol) was added. After stirring at room temperature for 5 days, precipitation of barbituric acid was observed. The reaction mixture was filtered and washed with sat. aq. NaHCO3 (1×40 mL), and brine (2×40 mL). The mixture was dried over Na2SO4, filtered, and the solvent was removed under reduced pressure. GC-MS analysis of the concentrate showed 2-bromo-3-phenylpropanal as the sole product. (2) Preparation of (61): N-(methyl(oxo){1-[6-(trifluoromethyl)-3-pyridinyl]ethyl}-λ6-sulfanylidene)thiourea (J) (100 mg, 0.321 mmol) was suspended in EtOH (1 mL) and 2-bromo-3-phenylpropanal (82 mg, 0.385 mmol, 1.2 eq) in EtOH (0.6 mL) was added. The reaction was stirred at r.t. for 1 h, and then heated to reflux for 30 min. The solvent was removed under reduced pressure and the residue purified by preparative reverse-phase column chromatography (water/acetonitrile). 5-{1-[(5-benzyl-1,3-thiazol-2-yl)(methyl)sulfonimidoyl]ethyl}-2-(trifluoromethyl)pyridine (61) was obtained in form of a yellowish oil (26 mg, 0.061 mmol, 19%) as a racemate and 1:1 mixture of diastereomers. 1H-NMR (CDCl3, 400 MHz): δ=1.89 (d, J=7.2 Hz, 1.5H, CHCH3, diastereomer 1); 1.92 (d, J=7.2 Hz, 1.5H, CHCH3, diastereomer 2); 3.09 (s, 1.5H, S—CH3, diastereomer 1); 3.20 (s, 1.5H, S—CH3, diastereomer 2); 3.94 (s, 1H, CH2Ph, diastereomer 1), 3.97 (s, 1H, CH2Ph, diastereomer 2); 5.14 (q, J=7.2 Hz, 0.5H, CHCH3, diastereomer 1); 5.21 (q, J=7.2 Hz, 0.5H, CHCH3, diastereomer 2); 6.90 (s, 0.5H, thiazole, diastereomer 1); 6.92 (s, 0.5H, thiazole, diastereomer 2); 7.15-7.37 (m, 5H, Ph); 7.71 (d, J=8.2 Hz, 0.5H, pyr-C3-H, diastereomer 1), 7.72 (d, J=8.2 Hz, 0.5H, pyr-C3-H, diastereomer 2); 8.09 (dd, 3J=8.2 Hz, 4J=1.8 Hz, 0.5H, pyr-C4-H, diastereomer 1); 8.12 (dd, 3J=8.2 Hz, 4J=1.7 Hz, 0.5H, pyr-C4-H, diastereomer 2); 8.75 (d, 4J=1.8 Hz, 0.5H, pyr-C6-H, diastereomer 1); 8.79 (d, 4J=1.8 Hz, 0.5H, pyr-C6-H, diastereomer 2); 13C-NMR (CDCl3, 100 MHz): δ=13.8, 14.2 (CHCH3, two diastereomers); 33.2. 33.3 (CH2Ph, two diastereomers); 36.5, 36.8 (S—CH3, two diastereomers); 60.8, 61.6 (CHCH3, two diastereomers); 119.5, 119.6 (pyr-C, 2 diastereomers); 125.6, 125.7 (Ph, two diastereomers), 127.2, 127.3 (Ph, two diastereomers, 127.5 (Ph, two diastereomers), 130.1, 130.2 (pyr-C, two diastereomers), 131.1, 131.5, (pyr-C, two diastereomers), 132.7, 133.2 (thiazole, two diastereomers), 137.3, 137.6 (pyr-C, 2-diastereomers); 137.9, 138.0 (thiazole, two diastereomers); 149.2, 149.4 (pyr-C, 2-diastereomers); 165.6, 165.8 (thiazole, two diastereomers); CF3, not detected. UPLC-MS (ESI+): mass calc'd for C19H19F3N3OS2 (M+H+): 426.1. Found 426.1, UPLC-MS (ESI−) mass calc'd for C19H17F3N3OS2 (M−H+): 424.1. Found 424.1.

1. customprecipitation of barbituric acid
2. filtrationThe reaction mixture was filtered
3. washwashed with sat. aq. NaHCO3 (1×40 mL), and brine (2×40 mL)
4. dry with materialThe mixture was dried over Na2SO4
5. filtrationfiltered
6. customthe solvent was removed under reduced pressure
7. custom(2) Preparation of (61)
8. stirringThe reaction was stirred at r.t. for 1 h
9. temperatureheated
10. temperatureto reflux for 30 min
11. customThe solvent was removed under reduced pressure
12. customthe residue purified by preparative reverse-phase column chromatography (water/acetonitrile)

ORD record

ord-aae77fcbcdc34efb9d813c0c0bbbc0d9

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08288589B2