Novel method for preparing 7-amino clonazepam compound

A technology of aminochloride and compounds, applied in the direction of organic chemistry, etc., can solve problems such as troublesome disposal and large environmental impact

A technology of aminochloride and compounds, applied in the direction of organic chemistry, etc., can solve problems such as troublesome disposal and large environmental impact

CN113072508APending Publication Date: 2021-07-06CHENGDU ORGANIC CHEM CO LTD CHINESE ACAD OF SCI
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  • Novel method for preparing 7-amino clonazepam compound
  • Novel method for preparing 7-amino clonazepam compound
  • Novel method for preparing 7-amino clonazepam compound

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Embodiment 1

[0043] A method for synthesizing 7-aminoclonazepam compound, comprising the following steps:

[0044] (1) Synthesis of intermediate I:

[0045]

[0046] Weigh 2-amino-4-nitrobenzoic acid (5.46g, 30mmol) and transfer it to a 250mL flask, add 80mL of acetic anhydride, then heat to reflux and react for 12h. Cool to room temperature, filter, and rinse the obtained solid with a petroleum ether-ethyl acetate mixture to obtain 5.75 g of intermediate I as a light yellow solid, with a yield of 93%;

[0047] (2) Synthesis of Intermediate II:

[0048]

[0049] Weigh intermediate I (4.12g, 20mmol), dissolve it in 80mL, add 2-chlorophenylmagnesium bromide (40mmol, 1mol / L tetrahydrofuran solution) dropwise under ice-water bath, remove the ice-water bath after 20 minutes , after the reaction is complete, add 30 mL of saturated ammonium chloride solution to quench the reaction, separate the layers, collect the organic phase, extract the water phase (30 mL*2), combine the organic phase...

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Abstract

The invention discloses a novel method for preparing a 7-amino clonazepam compound, and belongs to the technical field of organic synthesis. The preparation method comprises the steps that 2-amino-4-nitrobenzoic acid serves as an initial raw material, and a target compound is obtained through the processes of acetyl-lactonization, Grignard reaction, amide hydrolysis, intramolecular condensation reaction, reduction and the like. The method provided by the invention is safe to operate, avoids the use of heavy metals, is simple and convenient in post-treatment, can obtain the product through direct filtration and recrystallization, and does not need other purification. Only conventional acid, alkali and solvents are used in the whole reaction process, so that the method is less in environmental pollution, low in cost and higher in yield.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to a novel method for preparing 7-aminoclonazepam compounds. Background technique [0002] Clonazepam belongs to benzodiazepines, which was approved by the US Food and Drug Administration (FDA) in 1975. Its effect is similar to that of diazepam (stable), but its anticonvulsant effect is 5 to 10 times stronger than that of diazepam. It has obvious and rapid effects on hypnosis, anti-anxiety, epilepsy and convulsions. As its metabolite, 7-aminoclonazepam is essential for its research. [0003] At present, there are few reports about the synthesis method of 7-aminoclonazepam. Documents Steiger.N., Sach.G., J.Med.Chem.1963, 6, 3, 261–265. reported that the product was directly nitrated and then reduced, but the problem of selectivity was involved, and the specific operation was more complicated. difficulty. [0004] [0005] In addition, EP2687854A1 discloses a para-sub...

Claims

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Application Information

Patent Timeline
06 Jul 2021
Publication
CN113072508A
IPC
C07D243/24; C07D243/28
CPC
C07D243/24; C07D243/28
Inventors
袁伟成; 王浩宇