Reaction Steps
A suspension of 3-benzothiazol-2-yl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyridin-2-ylamine (BB8) (95.6 mg, 0.271 mmol, 1.2 eq), 3-(4-iodopyrazol-1-yl)-8-methyl-8-azabicyclo[3.2.1]octane (69.1 mg, 0.218 mmol, 1.0 eq), (1,1′-bis-(diphenylphosphino)-ferrocene) palladium dichloride (16.0 mg, 0.0219 mmol, 10 mol %), and K2CO3 (92.0 mg, 0.666 mmol, 3 eq) in a 4:1 ratio of DME to H2O (2.5 mL) was evacuated and charged with nitrogen several times, after which the sample was heated in the microwave reactor to 80° C. for 30 min. The reaction mixture was partitioned between EtOAc and water and the layers were separated. The aqueous layer was back extracted with EtOAc (3×) and the combined organic layers were washed with water (1×) and brine (1×), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to dryness. The emulsion that had formed was collected separately and extracted with CH2Cl2 (2×), washed with brine (1×), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. All organics were combined. The crude material was adsorbed onto silica gel and purified by column chromatography on silica gel [10″×0.5″ column, eluting with neat EtOAc→7N NH3(MeOH):EtOAc 2%→3%→5%]. Fractions containing product were pooled and concentrated in vacuo. The product was recrystallized from neat acetonitrile [heated until boiling, cooled to −20° C. for 16 h], giving the title material as a yellow solid. 1H NMR (400 MHz, CDCl3): δ=1.72-1.79 (m, 2H), 2.05 (ddd, J=13.1, 5.8, 3.3 Hz, 2H), 2.13-2.25 (m, 4H), 2.40 (s, 3H), 3.29-3.40 (m, 2H), 4.49-4.63 (m, 1H), 7.12 (br s, 2H), 7.39-7.44 (m, 1H), 7.50 (ddd, J=8.2, 7.2, 1.3 Hz, 1H), 7.71 (s, 1H), 7.72 (s, 1H), 7.92 (dd, J=7.9, 0.6 Hz, 1H), 7.99 (d, J=2.0 Hz, 1H), 8.02 (dd, J=8.1, 0.5 Hz, 1H), 8.32 (d, J=2.0 Hz, 1H). MS (ES+): m/z=417.13 (24) [MH+]. HPLC: tR=2.12 min (ZQ2, polar—5 min).
