These common heterocyclic compound, 591769-05-0, name is 3-Cyclopentylacrylonitrile, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Computed Properties of C8H11N
(3R)- and (3S)-3-Cyclopentyl-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile[0112] To a solution of 4-(1H-pyrazol-4-yl)-7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]-pyrimidine(15.0 g, 0.0476 mol) in ACN (300 mL) was added 3-cyclopentylacrylonitrile (15 g, 0.12 mol) (as a mixture of cisand trans isomers), followed by DBU (15 mL, 0.10 mol).The resulting mixture was stirred at room temperatureovernight. The ACN was evaporated. The mixture wasdiluted with ethyl acetate, and the solution was washedwith 1.0 N HCl. The aqueous layer was back-extractedwith three portions of ethyl acetate. The combined organic extracts were washed with brine, dried over sodiumsulfate, filtered and concentrated. The crude product waspurified by silica gel chromatography (gradient of ethylacetate/hexanes) to yield a viscous clear syrup, whichwas dissolved in ethanol and evaporated several timesto remove ethyl acetate, to afford 19.4 g of racemic adduct (93percent). The enantiomers were separated by preparative-HPLC, (OD-H, 15percent ethanol/hexanes) and usedseparately in the next step to generate their corresponding final product. The final products (see Step 3) stemming from each of the separated enantiomers were foundto be active JAK inhibitors; however, the final productstemming from the second peak to elute from the preparative-HPLC was more active than its enantiomer.1H NMR (300 MHz, CDCl3): delta8.85 (s, 1H), 8.32 (s, 2H),7.39 (d, 1H), 6.80 (d, 1H), 5.68 (s, 2H), 4.26 (dt, 1H), 3.54(t, 2H), 3.14 (dd, 1H), 2.95 (dd, 1H), 2.67-2.50 (m, 1H),2.03-1.88 (m, 1H), 1.80-1.15 (m, 7H), 0.92 (t, 2H), -0.06(s, 9H); MS(ES):437 (M+1).
The synthetic route of 3-Cyclopentylacrylonitrile has been constantly updated, and we look forward to future research findings.
Reference:
Patent; Incyte Holdings Corporation; FRIEDMAN, Paul A.; FRIDMAN, Jordan S.; LUCHI, Monica E.; WILLIAMS, William V.; (27 pag.)EP2349260; (2016); B1;,
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