Isopropanol → HCID 44124820, compound

Participants

Reaction Conditions

Reaction Steps

A vial containing (R)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazole (Example 64A, 31 mg, 0.074 mmol), methyl 6-bromo-2-pyridinecarboxylate (16 mg, 0.074 mmol), K2CO3 (31 mg, 0.22 mmol) and bis(triphenylphosphine)palladium(II) chloride (5 mg, 7 μmol) suspended in isopropanol (1 mL) was heated to 80° C. for 2 hours. The mixture was allowed to stand at room temperature over night. The mixture was partitioned between 1 M NaOH (5 mL) and CH2Cl2 (25 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (25 mL). The combined CH2Cl2 layers were dried (MgSO4), filtered, concentrated and chromatographed on silica gel eluting with a gradient of 2% to 10% (9:1 methanol:ammonium hydroxide) in CH2Cl2 and then rechromatographed on silica gel eluting with a gradient of 10:1:1 to 7:1:1 ethyl acetate:HCO2H:H2O. The residue was partitioned between 1 M NaOH and CH2Cl2. This CH2Cl2 layer was dried (MgSO4), filtered and concentrated to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.42-1.52 (m, 2H), 1.44 (d, J=6.3 Hz, 6H), 1.59-1.68 (m, 4H), 1.96-2.11 (m, 1H), 2.26-2.36 (m, 1H), 2.41-2.59 (m, 4H), 2.95-3.08 (m, 1H), 3.46 (t, J=9.3 Hz, 1H), 3.53-3.63 (m, 1H), 3.75-3.84 (m, 1H), 3.85-3.94 (m, 1H), 5.29-5.39 (m, 1H), 7.64 (d, J=8.7 Hz, 1H), 7.80-7.99 (m, 4H), 8.50 (d, J=1.2 Hz, 1H); MS (DCI/NH3) m/z 451 (M+H)+.

Provenance & Evidence