Reference of 15861-23-1,Some common heterocyclic compound, 15861-23-1, name is Indoline-5-carbonitrile, molecular formula is C9H8N2, 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.
A mixture of 4-(6-chloro-pyrimidin-4-yloxy)-piperidine-1 -carboxylic acid isopropyl ester (50.4 mg, 0.168 mmol) and 2,3-dihydro-1 H-indole-5-carbonitrile (22.0 mg, 0.15 mmol) in anhydrous 1 ,4-dioxane (2.0 ml.) was heated to 105 degrees Celsius. After stirring for 5 min, a 1 M solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (0.184 ml_, 0.184 mmol) was added. After 30 minutes, the reaction mixture was quenched with saturated aqueous ammonium chloride and concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane and washed with saturated aqueous sodium bicarbonate. The aqueous phase was extracted three times with dichloromethane, and the combined organic layers were dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the crude residue was purified by column chromatography (20-60% ethyl acetate in heptane) to afford isopropyl 4-{[6-(5-cyano-2,3-dihydro-1 H-indol-1 -yl)pyrimidin-4-yl]oxy}piperidine-1 – carboxylate (38 mg, 61 %) as a white solid. 1H NMR (400 MHz, deuterochloroform) delta 1.25 (d, J=6.25 Hz, 6 H) 1.68 – 1.78 (m, 2 H) 1.96 – 2.04 (m, 2 H) 3.24 – 3.36 (m, 4 H) 3.78 – 3.87 (m, 2 H) 4.03 (t, J=8.79 Hz, 2 H) 4.89 – 4.97 (m, 1 H) 5.29 – 5.36 (m, 1 H) 5.96 (s, 1 H) 7.43 (s, 1 H) 7.51 (dd, J=8.79, 1.17 Hz, 1 H) 8.48 – 8.53 (m, 2 H). LCMS (ES+): 408.4 (M+1 ).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Indoline-5-carbonitrile, its application will become more common.
Reference:
Patent; PFIZER INC.; DAROUT, Etzer; DENINNO, Michael, Paul; FUTATSUGI, Kentaro; GUIMARAES, Cristiano, Ruch, Werneck; LEFKER, Bruce, Allen; MASCITTI, Vincent; MCCLURE, Kim, Francis; MUNCHHOF, Michael, John; ROBINSON, Ralph, Pelton, Jr.; WO2010/128414; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem