Sodium Iodide → (3aR,7aR)-2,2-dimethyl-3-(6-((5-(oxetan-3-yloxy)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)octahydrobenzo[d]oxazole

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of 1-((2-((3aR,7aR)-2,2-dimethylhexahydrobenzo[d]oxazol-3(2H)-yl)benzo[d]thiazol-6-yl)methyl)-1H-benzo[d]imidazol-5-ol (100 mg, 0.23 mmol) from Step 1 of Example 171, oxetan-3-yl 4-methylbenzenesulfonate (420 mg, 1.84 mmol) from the previous step, Cs2CO3 (225 mg, 0.69 mmol), sodium iodide (276 mg, 0.69 mmol) and NMP (4 mL) was heated at 145° C. for 15 h. The mixture was diluted with EtOAc and washed with brine. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with 40:1 DCM/MeOH to afford (3aR,7aR)-2,2-dimethyl-3-(6-((5-(oxetan-3-yloxy)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)octahydrobenzo[d]oxazole (35 mg, 31%) as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.90 (s, 1H), 7.58 (d, J=8.4 Hz, 1H), 7.40 (s, 1H), 7.17-7.20 (m, 2H), 6.94 (s, 1H), 6.84 (m, 1H), 5.35 (s, 2H), 5.24 (m, 1H), 5.00 (m, 2H), 4.79 (m, 2H), 3.66 (m, 1H), 3.08 (m, 1H), 2.81 (m, 1H), 2.15 (m, 1H), 1.84-1.92 (m, 2H), 1.78 (s, 3H), 1.63 (s, 3H), 1.30-1.45 (m, 4H); LCMS (ESI) m/z 491 (M+H)+.

Provenance & Evidence