Background and overview of the preparation method of 1,1-thiocarbonyl DI-2(1H)-pyridine
1,1-Thiocarbonyl DI-2(1H)-pyridine is a heterocyclic organic compound that can be used as a pharmaceutical synthesis intermediate.
Preparation method of 1,1-thiocarbonyl DI-2(1H)-pyridine Preparation method
1,1-Thiocarbonyl DI-2(1H)-pyridine can be used to prepare compound I, which can be used to prepare and treat drugs for fibrotic diseases:
1) Compound II: Dissolve compound F (114.00mg, 315.13μmol) in dioxane (10mL), add 1,1-thiocarbonyl DI-2(1H)-pyridine (102.47mg, 441.18 μmol), the reaction was stirred at 101°C for 16 hours. Afterwards, the reaction was cooled to 25°C, and cyclopropylamine (395.78 mg, 6.93 mmol) was added. After the reactant was stirred at 25°C for 16 hours, it was directly separated by preparative chromatography (synergimax-RP, 200*25mm, 4um, trifluoroacetic acid) to obtain the target compound II (light yellow solid, 16.30 mg, yield 9.00%).
1HNMR (MHz, CD3OD) 9.05 (s, 1H), 8.95 (d, J=6.4Hz, 1H), 7.86-7.72 (m, 1H), 7.66 (s, 1H), 7.55-7.51 (m, 1H), 7.22(m, 2H), 4.22(s, 3H), 2.76(m, 1H), 0.94(m, 2H), 0.79(m, 2H).
2) Compound I: Add 300mL ethanol into a 500mL three-necked flask at 20-30℃, and slowly (2 drops/second) drop methanesulfonic acid (2.50g, 26.04mmol) at 20-30℃ Add to the three-necked flask; heat the reaction flask to 55~60°C (internal temperature), add compound G (10.00g, 21.70mmol) to R1; after adding, stir at 55~60°C (internal temperature) for 1 minute, then slowly (40~50 minutes) Cool to 20~25℃, stir at 20~25℃ for 14 hours; filter, wash the filter cake with ethanol (5mL*2); vacuum dry the filter cake at 45~50℃ for 4 hours, HNMR (P05222- 001-P1A) detection; vacuum drying at 75-80°C for 14 hours, HNMR detection; obtain the product compound I (off-white solid, 1 sodium bicarbonate 0.02g);
1HNMR (MHz, DMSO-d6) δppm9.39 (s, 1H) 8.99-9.15 (m, 1H) 8.75 (s, 1H) 8.36 (brs, 1H) 7.89-8.08 (m, 2H) 7.87-7.88 (m, 1H) 7.82 (brs, 1H) 7 Bismuth subcarbonate.55-7.72 (m, 2H) 7.06 (brs, 1H) 4.11 (s, 3H) 2.38 (s, 3H) 0.48-0.93 (m, 4H )
