Adding a certain compound to certain chemical reactions, such as: 32779-36-5, 5-Bromo-2-chloropyrimidine, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound, Computed Properties of C4H2BrClN2, blongs to pyrimidines compound. Computed Properties of C4H2BrClN2
To a solution of THF (2000.0 ml) and sodium hydride (17.0 gm, 0.708 mol), was added A/-5-(4-bromophenyl)-6-(-2-hydroxyethoxy)-4-pyrimidinyl-//- propylsulfamide (100.0 gm, 0.23 mol) at 25-30°C. Stirred the content for 30 min at 25-30° C. DMF (400.0 ml) and 5-bromo-2-chloro-pyrimidine (65.0 gm; 0.033 mol) was added to the reaction mass at 25-30° C. Stirred and heated reaction mass to 60-65°C and maintain the reaction mass at 60-65° C for 2-4 hr. After completion of reaction monitored by HPLC, cooled the reaction mass to 25-30° C and 5percent w/v citric acid solution (2500.0 ml) was added. The compound was extracted twice with ethyl acetate (1500.0 ml x 2), followed by organic layer was washed with 10percent w/v brine solution (1500.0 ml). Ethyl acetate layer was concentrated at 55-60°C under reduced pressure to produce A/-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy] ethoxy]-4-pyrimidinyl]-/V-propylsulfamide as a crude residue. Obtained residue was dissolved at 65-70°C in methanol (2400.0 ml), stirred and maintained for 30 min. The resulting solution was gradually cooled to room temperature then cooled to 0-5°C and maintained reaction mass at 0-5°C for 45-60 min. Obtained solid was filtered, washed with methanol (100.0 ml), suck dried to afford crude /V-[5-(4-bromophenyl)-6-[2-[(5-bromo-2- pyrimidinyl)oxy] ethoxyJ^-pyrimidinylJ-Af-propylsulfamide [Macitentan]. [Yield = 121.5 gm; Purity (HPLC) = 99.68percent]. Purification of Macitentan ( I ) Macitentan crude (121.5 gm, 0.202 mol) wet solid was dissolved at 65-70°C in methanol (2400.0 ml) and decolorized with activated charcoal. The resulting solution was gradually cooled to room temperature then cooled to 0- 5°C and maintained for 45-60 min. Obtained solid was filtered, washed with methanol (100.0 ml), suck dried and dried under vacuum at 55-60°C to afford highly pure Macitentan. [Yield = 111.5 gm; Purity (HPLC) = 99.94percent]. (M + H)+/z= 589.0. 1H NMR (CDCIa): delta 8.49 (s, 2 H), 8.45 (s, 1H), 7.57-7.54 (m, 2H), 7.16-7.12 (m, 2H), 6.87 (s, 1 H), 5.60-5.57 (t, J = 6.24 Hz, 1 H), 4.71- 4.69 (m, 2H), 4.61-4.59 (m, 2H), 2.97-2.92 (q, 2H), 1.61-1.52 (h, J = 7.36 Hz, 2H), 0.94-0.91 (t, J = 7.36 Hz, 3H). 13C NMR (CDC ): delta 11.24, 21.97, 44.62, 64.68, 65.48, 104.80, 111.85, 121.31, 129.48, 131.35, 132.51 , 155.82, 156.41 , 159.68, 163.10, 165.75.
At the same time, in my other blogs, there are other synthetic methods of this type of compound,32779-36-5, 5-Bromo-2-chloropyrimidine, and friends who are interested can also refer to it.
Reference:
Patent; MEGAFINE PHARMA (P) LTD.; MATHAD Vijayavitthal Thippannachar; NIPHADE NAVNATH CHINTAMAN; KABRA SANJAY RAMESHWAR; JAGTAP KUNAL MADHAV; PAWAR ANIL RAMBHAU; (43 pag.)WO2016/203489; (2016); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia