Reference of 5767-35-1, In the chemical reaction process,reaction time,type of solvent,can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product.An updated downstream synthesis route of 5767-35-1 as follows.
Example 11 : Synthesis of (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-lH-l,2,4-triazol- -yl)-N’-(6-chloropyrimidin-4-yl)acrylohydrazide (1-12).A 25-mL, 3-necked, round-bottomed flask was charged with a solution of (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-lH-l,2,4-triazol-l-yl)acrylic acid (0.5 g) and 4-chloro-6- hydrazinopyrimidine (0.20 g, 1.0 eq.) in EtOAc (5.0 mL). The mixture was cooled at -40 C and treated with T3P (2.3 mL, 2.5 eq.) and DIPEA (0.98 mL, 4.0 eq.). TLC analysis (using 5% MeOH-CH2Cl2 as eluent) showed that the starting material was consumed after 30 min. The reaction mixture was then diluted with CH2O2, washed with water, dried over anhydrous Na2S04, filtered and concentrated under reduced pressure (25 C, 20 mmHg) to afford crude material that was subjected to preparative TLC purification using 5% MeOH-CH2Cl2 with as the mobile phase. This afforded 250 mg (yield: 36.74%) (Z)-3-(3-(3,5- bis(trifluoromethyl)phenyl)- 1 H- 1 ,2,4-triazol- 1 -yl)-N’-(6-chloropyrimidin-4-yl- )acrylohydrazide. 1H NMR (400 MHz, DMSO-d6), delta= 10.59 (br s, exchangeable, 1H), 9.85 (br s, exchangeable, 1H), 9.52 (s, 1H), 8.50 (s, 2H), 8.38 (s, 1H), 8.27 (s, 1H), 7.52-7.55 (d, 1H, J= 10.4 Hz), 6.69 (s, 1H), 6.05-6.08 (d, 1H, J= 10.4 Hz); LCMS: Calculated forCI7HII C1F6N70 (M+H)+ 478.76; found: 478.09 (RT 2.79 min, purity: 97.51%).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,5767-35-1, its application will become more common.
Reference:
Patent; KARYOPHARM THERAPEUTICS, INC.; SANDANAYAKA, Vincent, P.; SHACHAM, Sharon; MCCAULEY, Dilara; SHECHTER, Sharon; WO2013/19548; (2013); A1;,
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