Reaction Steps
To a solution of adamantanemethanol (1.2 g, 7.4 mmol) in DMF (8 mL) was added NaH (0.3 g, 7.4 mmol) in a single portion. After gas evolution subsided, 4-chloropyridine N-oxide (0.8 g, 6.17 mmol) was added. The reaction mixture was stirred at room temperature under Ar until the reaction was complete. The mixture was quenched with water and extracted with CH2Cl2. The organic layer was washed with H2O and 5% LiCl, dried over Na2SO4, filtered and concentrated to dryness. Purification by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2) gave 4-(adamantylmethoxy)pyridine N-oxide (1.55 g, 97%) as a yellow solid. This material was suspended in Ac2O (5 mL), heated to 140° C. and stirred at 140° C. for 4 h. After cooling, the mixture was diluted with CH3OH and H2O (10 mL, 1:1 mixture) and stirred at room temperature for 1 h. The mixture was concentrated, and the residue was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2) to give 4-(adamantylmethoxy)pyridin-2(1H)-one (1.08 g, 70%) as a brown solid. Following the procedure of Example 62 (step f), but substituting 5-bromo-1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazole for 4-(2-(5-iodo-1H-indazol-1-yl)ethyl)morpholine, 4-(adamantylmethoxy)pyridin-2(1H)-one for 4-phenethylpyridin-2(1H)-one, and 1,2-trans-cyclohexyldiamine for 8-hydroxyquinoline, the title compound (142 mg, 79%) was obtained as a yellow powder: mp 252-254° C.; 1H NMR (500 MHz, CD3OD) δ 8.24 (s, 1H), 7.82 (d, J=2.0 Hz, 1H), 7.78 (d, J=9.0 Hz, 1H), 7.58 (d, J=7.5 Hz, 1H), 7.46 (dd, J=9.0, 2.0 Hz, 1H), 6.29 (dd, J=7.5, 3.0 Hz, 1H), 6.04 (d, J=2.5 Hz, 1H), 4.87 (t, J=6.5 Hz, 2H), 3.86 (t, J=5.5 Hz, 2H), 3.69-3.72 (m, 2H), 3.63 (s, 2H), 3.16-3.20 (m, 2H), 2.16-2.19 (m, 2H), 2.00-2.03 (m, 3H), 1.71-1.84 (m, 12H), 1.24-1.31 (m, 2H); ESI MS m/z 473 [M+H]+; HPLC (Method D) 98.9% (AUC), tR=15.4 min.
