Method for synthesizing chiral dihydro-5H-pyrrolo[2,1-c][1,4]-benzodiazepino-5-one

[0036] Embodiment 1: optimization of conditions

[0037]In a nitrogen-filled glove box, (1,5-cyclooctadiene) iridium chloride dimer (0.0025 mmol, 1.7 mg) and one of the chiral ligands in the following formula (0.0055 mmol ) into a reaction flask with 1 mL of mixed solvent (the volume ratio of dichloromethane and toluene is 1:2), stirred at room temperature for 10 minutes, and then transferred the prepared catalyst to another container containing the raw material pyrrolo[2,1 -c] [1,4]-benzodiazepin-5-one 1a (38 mg, 0.125 mmol) and morpholine trifluoroacetate (2.5 mg, 0.0125 mmol) in a reaction vial, shared 3mL of mixed solvent (the volume ratio of dichloromethane and toluene is 1:2). The reaction bottle was placed in a stainless steel autoclave, and hydrogen gas was introduced at a pressure of 50 atmospheres, and the reaction was carried out at room temperature for 24 hours. Slowly release hydrogen, remove the solvent with a rotary evaporator, and then directly column chromat...

[0043] Example 2: Synthesis of various chiral dihydro-5H-pyrrolo[2,1-c][1,4]-benzodiazepine-5-ones by iridium-catalyzed asymmetric hydrogenation 2

[0044] In a nitrogen-filled glove box, (1,5-cyclooctadiene) iridium chloride dimer (0.0025 mmol, 1.7 mg) and chiral ligand (S, S, R)-C 3 *-TunePhos (0.0055 mmol) in the reaction bottle, add 1mL mixed solvent (the volume ratio of methylene chloride and toluene is 1: 2), stir at room temperature for 10 minutes, then transfer the prepared catalyst to another container containing The substrate pyrrolo[2,1-c][1,4]-benzodiazepin-5-one 1 (0.125 mmol) and morpholine trifluoroacetate (2.5 mg, 0.0125 mmol) In the reaction flask, 3 mL of mixed solvent (the volume ratio of dichloromethane and toluene is 1:2) is shared. The reaction bottle was placed in a stainless steel autoclave, and hydrogen gas was introduced at a pressure of 50 atmospheres, and the reaction was carried out at room temperature for 24 hours. Slowly release hydrogen, remov...