Reaction Steps
[8-Benzyl-10-(1H-imidazol-2-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (233 mg, 0.48 mmol) was suspended in a mixture of anhydrous DMF (1.5 mL)/THF (0.1 mL) under an atmosphere of nitrogen at 0° C. NaH (19 mg, 0.48 mmol) was added and the reaction mixture was stirred for 30 minutes, then MeI (68 mg, 30 μL, 0.48 mmol) was added and the reaction mixture was stirred for 10 minutes. The reaction mixture was quenched with water and diluted with EtOAc, the layers were separated and the aqueous layer was extracted once more with EtOAc. The combined organics were washed with brine solution (2×5 mL), dried over Na2SO4, filtered and concentrated in vacuo to an oil. The residue was purified by silica gel column chromatography using 0-5% MeOH in DCM to yield [8-benzyl-10-(1-methylimidazol-2-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (205 mg, 86%) as a white foam. ESI-MS m/z calc. 502.3. Found 503.1 (M+1)+; Retention time: 1.51 minutes (3 min run); 1H NMR (400 MHz, DMSO) δ 7.38-7.30 (m, 4H), 7.25 (ddd, J=8.4, 5.9, 2.2 Hz, 1H), 7.19 (d, J=7.0 Hz, 2H), 7.10 (d, J=1.1 Hz, 1H), 6.96 (t, J=5.9 Hz, 1H), 6.75 (d, J=1.1 Hz, 1H), 4.96 (ddd, J=9.9, 6.7, 2.4 Hz, 1H), 4.68-4.59 (m, 1H), 3.70 (s, 3H), 3.53 (td, J=13.6, 9.0 Hz, 3H), 3.30-3.15 (m, 2H), 2.93 (dd, J=11.1, 0.7 Hz, 1H), 2.74-2.69 (m, 1H), 2.66-2.52 (m, 2H), 2.13 (s, 3H), 1.95-1.86 (m, 1H), 1.61-1.33 (m, 4H), 1.28 (d, J=6.9 Hz, 6H).
