To a stirred mixture of 6-(chloromethyl)-2-(methylthio)benzo[d]thiazole (209 mg, 0.9 mmol) from Step 4 of Example 36 and 4-(1H-imidazol-4-yl)-1-methyl-1H-pyrazole (248 mg, 1.0 mmol) from Step 3 of this Example, in anhydrous DMF (3.0 mL) was added K2CO3 (700 mg, 5 mmol). After stirring for 3 h at 80° C., the reaction mixture was cooled to rt and partitioned between EtOAc (150 mL) and water (50 mL). The EtOAc layer was separated, washed with brine (50 ml), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified via silica gel flash chromatography (eluting isocratically with 1% MeOH in CH2Cl2) to afford separately 6-((5-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)methyl)-2-(methylthio)benzo[d]thiazole and 6-((4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)methyl)-2-(methylthio)benzo[d]thiazole as white solids. The first eluting regioisomer is referred to as regioisomer 1 (55 mg, 16%) and the second eluting regioisomer is referred to as regioisomer 2 (142 mg, 42%). The regiochemistry of the alkylation was examined by 2-dimensional nuclear Overhauser effect (NOE) experiment but was inconclusive. Regioisomer 1: 1H NMR (300 MHz, CDCl3) δ 7.81 (d, J=8.3 Hz, 1H), 7.60 (s, 1H), 7.37 (s, 1H), 7.31 (s, 1H), 7.19 (s, 1H), 7.08-7.14 (m, 2H), 5.23 (s, 2H), 3.85 (s, 3H), 2.78 (s, 3H). LCMS (ESI) m/z 342 (M+H)+. Regioisomer 2: 1H NMR (300 MHz, CDCl3) δ 7.81 (d, J=8.3 Hz, 1H), 7.60-7.71 (m, 2H), 7.47-7.56 (m, 2H), 7.22 (dd, J=1.6, 8.4 Hz, 1H), 6.94 (s, 1H), 5.15 (s, 2H), 3.87 (s, 3H), 2.76 (s, 3H). LCMS (ESI) m/z 342 (M+H)+.
