4-Aminotetrahydropyran hydrochloride → (R)-10-(3-hydroxy-3-(5-methylisoxazol-3-yl)but-1-yn-1-yl)-N3-(tetrahydro-2H-pyran-4-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2,3-dicarboxamide

関与物質

反応条件

反応手順

Similar to as described in Example 10 (carbonylative amidation) a mixture of 10-bromo-3-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide (200 mg, 0.46 mmol, 1.00 equiv), 4-aminotetrahydropyran hydrochloride (126 mg, 0.92 mmol, 2.00 equiv), Pd(dppf)Cl2 (34 mg, 0.05 mmol, 0.10 equiv), TEA (202 mg, 2.00 mmol, 4.00 equiv), and DMSO (5 mL) was stirred at 40° C. under an atmosphere of CO(g) overnight. The reaction was quenched with water and the solids were collected. This resulted in 250 mg (crude) of 10-bromo-N3-(tetrahydro-2H-pyran-4-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2,3-dicarboxamide as a brown solid. Similar to as described General Procedure F, 10-bromo-N3-(tetrahydro-2H-pyran-4-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2,3-dicarboxamide was reacted with (2R)-2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol to give the titled compound as an off-white solid (38.6 mg, 6.6%).

情報源と証拠