Electric Literature of 709652-82-4, 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 709652-82-4 as follows.
To a microwave vial equipped with a stirbar was dissolve 2-amino-5-bromonicotinonitrile (0.087 g, 0.44 mmol) in anhydrous acetonitrile (4 mL). To the solution was added potassium acetate(0.086 g, 0.86 mmol), 4,4,4?,4?,5,5,5?,5?-octamethyl-2,2?-bi(1,3,2-dioxaborolane (0.223 g, 0.86 mmol) and 1,1 ?-bis(diphenylphosphino)ferrocene-palladium(ll)dichloride (0.016 g, 0.022 mmol). The resulting mixture was microwaved at 150 C for 15 mm. To the mixture was added (1R,5S,6r)-6-(3-iodo- 1 -isopropyl- 1H-pyrazol-5-yl)-3-(oxetan-3-yl)-3-azabicyclo[3.1 .0]hexane (0.100 g, 0.26 mmol), 1M potassium carbonate (4 mL) and further1,1 ?-bis(diphenylphosphino)ferrocene-palladium(ll)dichloride (0.008 g, 0.011 mmol) and the resulting mixture was microwave at 110 C for 15 mm. The reaction mixture was diluted with 10 mL water and extracted with ethyl acetate (3 x 15 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated to dryness in vacuo. This crude material was purified by RP-HPLC affording2-amino-5-(1 -isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3. 1 .0]hexan-6-yl)-1H-pyrazol-3-yl)nicotinonitrile (20.1mg, 21%): ?H NMR (400MHz, DMSO-d6) oe: 8.57 (s, 1H), 8.08 (s, 1H), 6.91(s, 2H), 6.35 (s, 1H), 4.73 -4.62 (m, 1H), 4.60-4.44 (m, 4H), 3.81 – 3.70 (m, 1H), 3.12 (d, J = 8.8Hz, 2H), 2.46-2.39 (m, 2H), 2.19-2.12 (m, 1H), 1.82- 1.76 (m, 2H), 1.42 (d, J = 6.5 Hz, 6H).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,709652-82-4, its application will become more common.
Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; ESTRADA, Anthony; LIU, Wen; PATEL, Snahel; SIU, Michael; WO2014/111496; (2014); A1;,
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