ChemicalBook CAS DataBase List Verdinexor (KPT-335)

Verdinexor (KPT-335) synthesis

5synthesis methods

Product Name:Verdinexor (KPT-335)
CAS Number:1392136-43-4
Molecular formula:C18H12F6N6O
Molecular Weight:442.32

4930-98-7 Synthesis

4930-98-7
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(Z)-3-(3-(3,5-bis(trifluoroMethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid

1388842-44-1
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1392136-43-4
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$39.00/1mg

Yield: 48%

Reaction Conditions:

with 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide;N-ethyl-N,N-diisopropylamine in dichloromethane;ethyl acetate at -40; for 0.5 h;

Steps:

3 Example 3: Synthesis of (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-lH-l,2,4- -yl)-N'-(pyridin-2-yl)acrylohydrazide hydrochloride (1-4)
Example 3: Synthesis of (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-lH-l,2,4- -yl)-N'-(pyridin-2-yl)acrylohydrazide hydrochloride (1-4).A 500-mL, 3 -necked, round-bottomed flask was charged with a suspension of (Z)-3- (3-(3,5-bis(trifluoromethyl)phenyl)-lH-l ,2,4-triazol-l-yl)acrylic acid (10 g, 1.0 eq.) in 1 : 1 CH2C12:AcOEt (200 mL). 2-Hydrazinopyridine (3.1 1 g) was added at -40°C. T3P (50% in ethylacetate) (21.75 g) was added dropwise followed by DIPEA (7.36 g) and the reaction mixture was stirred for 30 min at -40 °C before being concentrated under reduced pressure (35 °C, 20 mm Hg) to afford a crude brown oil that was purified by column chromatography (the compound eluted with 1.3% MeOH in CH₂C1₂). Fractions containing desired compound were combined to afford 6.0 g (yield: 48%) (Z)-3-(3-(3,5-bis-(trifluoromethyl)phenyl)-lH- 1 ,2,4-triazol- 1 -yl)-N'-(pyridin-2-yl)acrylohydrazide. 1H NMR (400MHz, DMSO-d6) δ ,10.41(s, 1H), 9.66 (s, 1H), 8.59 (s, 1H), 8.53 (s, 2H), 8.28 (s, 1H), 8.06-8.08 (d, J=5.2 Hz, 1H), 7.48-7.53 (m, 1H), 7.49-7.52 (d, J=10.4, 1H), 6.71-6.75 (m, 1H), 6.66-6.68 (d,J=8.4Hz,lH), 6.07-6.09 (d, J=10.4, 1H). LCMS for Ci₈Hi₂F₆N₆0 [M+H]⁺ predicted: 443.33, found: 443.44 (RT 2.45 min, purity: 100%).

References:

Location in patent:Page/Page column 57