KPT-330, (E)-RN Chemical Properties

Density 

1.55±0.1 g/cm3(Predicted)

solubility 

DMSO: Soluble

pka

9.74±0.43(Predicted)

KPT-330, (E)-RN Usage And Synthesis

Uses

KPT-330 is an orally bioavailable selective?Chromosome Region Maintenance (CRM1)?inhibitor, that has been shown to block pancreatic cancer cell proliferation and reduce tumor growth in mice.

Synthesis

General procedure for the synthesis of (E)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N'-(pyrazin-2-yl)acrylhydrazide from the compound (CAS: 1421923-96-7) and pyrazin-2-hydrazine: 1. a solution was prepared by dissolving (E)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (0.75 g) in EtOAc (25 mL) and THF (12.5 mL). 2. To the above solution, a solution of 2-hydrazinopyrazine (0.23 g) in THF (12 mL) was added dropwise at room temperature. 3. Subsequently, T3P (50% ethyl acetate solution, 1.52 mL) and DIPEA (1.46 mL) were added dropwise and the reaction mixture was stirred at room temperature for 30 minutes. 4. After completion of the reaction, the reaction was quenched with ice-cold water and extracted with EtOAc (3 x 25 mL). 5. The organic layers were combined, washed with brine and dried over anhydrous Na2SO4. 6. concentrated under reduced pressure (35 °C, 20 mmHg) to give 0.698 g of crude product. 7. The crude product was first ground with petroleum ether and then with Et2O to give 275 mg (yield: 29%) of the target compound. Product characterization: 1H NMR (400 MHz, DMSO-d6) δ: 10.3 (s, 1H), 9.15 (s, 2H), 8.59 (s, 2H), 8.30-8.26 (d, J = 14.8 Hz, 1H), 8.13 (s, 1H), 8.06-8.07 (m, 1H), 6.98-6.95 (d, J = 13.4 Hz. 1H); LCMS for C17H12F6N7O [M + H]+: 443.31; found: 444.19 (retention time: 2.625 min, purity: 99.06%).

References

[1] Patent: WO2013/19548, 2013, A1. Location in patent: Page/Page column 71-72
[2] De Souza, F.I., Zumiotti, A.V., and Da Silva, C.F. Neuregulins 1-α and 1-β on the regeneration the peripheral nerves[J]. Acta Ortop Bras.

KPT-330, (E)-RN(1421923-86-5)Related Product Information

• Selinexor
• PD 173074
• (Z)-3-(3-(3,5-bis(trifluoroMethyl)phenyl)-1H-1,2,4-triazol-1-yl)-1-(3,3-
• Verdinexor (KPT-335)