Method for synthesizing chiral dihydro-6H-benzpyrole-[2,1-c][1,4]-benzodiazepine-6-ketone

A technology of benzodiazepine and indoline, applied in the synthesis of chiral dihydro-6H-indolo[2,1-c][1,4]-benzodiazepine-6-one It can solve the problems of no literature reports in synthetic research, and achieve the effect of chiral value-added, complete reaction, and simple reaction operation

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A technology of benzodiazepine and indoline, applied in the synthesis of chiral dihydro-6H-indolo[2,1-c][1,4]-benzodiazepine-6-one It can solve the problems of no literature reports in synthetic research, and achieve the effect of chiral value-added, complete reaction, and simple reaction operation

CN103288831AInactive Publication Date: 2013-09-11DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI

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Embodiment 1

[0037] Example 1: Synthesis of various chiral dihydro-indolo[2,1-c][1,4]-benzodiazepin-6-ones by iridium-catalyzed asymmetric hydrogenation 2

[0038] 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 Starting materials indolo[2,2-c][1,4]-benzodiazepine-6-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...

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Abstract

The invention discloses a method for synthesizing chiral dihydro-6H-benzpyrole-[2,1-c][1,4]-benzodiazepine-6-ketone by asymmetric hydrogenation under catalysis of iridium. The reaction conditions are that the temperature is 0-50 DEG C; a solvent adopts a dichloromethane and methylbenzene mixed solvent in which the volume ratio of dichloromethane to methylbenzene is 1 to 2; the pressure is 13-50 atm; the proportion of a primer to a catalyst is 50 to 1; the catalyst is a complex consisting of (1,5-cyclooctadiene) iridium chloride dimer and diphosphine; an additive is morpholine trifluoroacetate or piperidine hydrochloride; a corresponding chiral dihydro product is obtained by hydrogenating seven-membered ring-shaped benzpyrole-[2,1-c][1,4]-benzodiazepine-6-ketone; enantiomer is excessive and can reach 96 percent. The method is easy to operate and practicable; raw materials are readily available; the enantioselectivity is high; the yield is high.

Description

technical field [0001] The present invention relates to a highly enantioselective catalytic hydrogenation of indolo[2,1-c][1,4]-benzodiazepine-6-one using a homogeneous system of iridium to synthesize chiral dihydro- Process for indolo[2,1-c][1,4]-benzodiazepin-6-ones, specifically an iridium-catalyzed asymmetric hydrogenation to chiral dihydro-6H-indoles and[2,1-c][1,4]-benzodiazepine-6-one method. technical background [0002] Indolo[2,1-c][1,4]-benzodiazepin-6-ones are a class of seven-membered heterocyclic compounds with a wide range of physiological and pharmacological activities, which exist in some natural products and Among pharmaceutical intermediates, it has high research value and application prospect. These compounds have a variety of potential biological activities, such as: anti-cancer, anti-inflammatory, sedative, hypnotic and anti-nervous properties. [0003] At present, there are very few reports on the synthesis of dihydro-indolo[2,1-c][1,4]-benzodiazepi...

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Application Information

Patent Timeline

11 Sep 2013

Publication

CN103288831A

IPC: C07D487/04; C07B53/00

Inventors: 周永贵; 高凯