Dimethylformamide → 8-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-[1,6]naphthyridine

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Reaction Conditions

Reaction Steps

Add 8-bromo-[1,6]naphthyridine (Spec; 32 mg, 0.152 mmol), 2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid (Preparation 5; 35 mg, 0.153 mmol), and potasium phosphate (97 mg, 0.458 mmol) to DMF (1 mL) and water (0.5 mL). De-gas the solution with argon and add tetrakis(triphenylphosphine)palladium(0) (88 mg, 0.076 mol). Heat the mixture at 60° C. for 18 h under an argon atmosphere. Cool the mixture to room temperature and dilute with water. Filter the mixture, and separate the filtrate. Extract the aqueous layer with dichloromethane. Dry the combined organic layers over sodium sulfate, filter, and concentrate. Purify the crude residue by column chromatography (12 g Redisep column, gradient dichloromethane through CMA over 40 min, 20 mL/min) to provide the title compound (31 mg, 64%) as an off white solid. Mp 180-184° C. MS (APCI) m/e=314 (M+1). 1H NMR (CDCl3) δ 8.88 (dd, J=1.6, 4.2 Hz, 1H), 8.60 (d, J=4.7 Hz, 1H), 8.28 (d, J=8.5 Hz, 1H), 8.19 (d, J=8.9 Hz, 1H), 7.73-7.68 (m, 3H), 7.58 (dd, J=4.2, 8.5 Hz, 2H), 4.30 (t, J=7 Hz, 2H), 3.30 (t, J=7 Hz, 2H), 2.73 (p, J=7 Hz, 2H). HPLC: >99%, Rt=7.1 min.

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