Method for synthesizing cinacalcet

A technology of cinacalcet and compounds, applied in the field of pharmaceutical chemical synthesis, can solve the problems of high synthesis cost, residue, complicated operation, etc., and achieve the effect of simple synthesis method, avoiding residue, and easy availability of raw materials

Inactive Publication Date: 2015-09-23
UNIV OF SCI & TECH OF CHINA
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0011] However, there are long routes (such as the above-mentioned route 1 and route 2) in these methods, and the operation is complicated
In addition, although the above route 3 achieves one-step synthesis, the yield is lower than 80%. In addition, it needs to use the noble metal platinum to participate in the catalysi

Method used

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  • Method for synthesizing cinacalcet
  • Method for synthesizing cinacalcet
  • Method for synthesizing cinacalcet

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Add 0.005mmol tris(pentafluorophenyl)boron to a 10mL Schlenk reaction tube (Beijing Shinwell Glass Instrument Co., Ltd., F891410 reaction tube, capacity 10mL, ground 14 / 20), replace the air in the tube with argon, and then Under an argon atmosphere, add 1.5 mL of n-butyl ether and 2.0 mmol of phenylsilane and stir (use IKA magnetic stirrer, RCT basic type, stirring speed 500 rpm). Then 0.5 mmol of (R)-1-(1-naphthyl)ethylamine and 1.0 mmol of 3-(3-trifluoromethylphenyl)propionic acid were added. After heating at 120° C. for 10 h, it was cooled to room temperature. Quenched with sodium hydroxide solution (3M; 3mL), added ethyl acetate (3mL), stirred at room temperature for 3h, extracted with ethyl acetate (2mL x 3), dried the organic phase with anhydrous sodium sulfate, filtered, and the organic phase Concentrate through a rotary evaporator (Buchi Co., Ltd., Switzerland, BUCHI rotary evaporator R-3), and then pass through a chromatography column (Beijing Xinweier Glass I...

Embodiment 2

[0060] The same procedure as Example 1 was followed, except that the reaction mixture was heated at 120° C. for 18 h and then cooled to room temperature. After the same post-treatment, a white crystal product was isolated with a yield of 81%.

[0061] After proton nuclear magnetic resonance spectrum, carbon nuclear magnetic resonance spectrum and fluorine nuclear magnetic resonance spectrum analysis, it was confirmed that the resulting product was N-((1R)-1-(1-naphthyl)ethyl)-3-(3-(trifluoromethyl) ) phenyl) propan-1-amine, namely cinacalcet.

Embodiment 3

[0063] The same procedure as Example 1 was followed, except that the reaction mixture was heated at 120° C. for 20 h and then cooled to room temperature. After the same post-treatment, a white crystal product was isolated with a yield of 88%.

[0064] After proton nuclear magnetic resonance spectrum, carbon nuclear magnetic resonance spectrum and fluorine nuclear magnetic resonance spectrum analysis, it was confirmed that the resulting product was N-((1R)-1-(1-naphthyl)ethyl)-3-(3-(trifluoromethyl) ) phenyl) propan-1-amine, namely cinacalcet.

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Abstract

The invention provides a method for synthesizing cinacalcet. According to the method, (R)-1-(1-naphthyl)ethylamine and 3-(3-trifluoromethylphenyl)propionic acid are adopted as raw materials; a nonmetal boron compound is adopted as a catalyst; an organosilane compound is adopted as a reducing agent; and a target product is synthesized with one step through a reductive coupling process. The method provided by the invention is simple and is easy to operate; and the raw materials are easy to obtain, such that cost is low. Also, no metal catalyst is needed in the synthesis process, such that metal residue in the drug is avoided, and the method is safe and environment-friendly. The method meets the requirements of green chemistry.

Description

technical field [0001] The invention relates to the field of pharmaceutical chemical synthesis, in particular to a method for synthesizing Cinacalcet. Background technique [0002] The chemical name of cinacalcet is: N-((1R)-1-(1-naphthyl)ethyl)-3-(3-(trifluoromethyl)phenyl)propan-1-amine, its structure represented by the following formula (III): [0003] [0004] The traditional treatment of secondary hyperparathyroidism (secondary hyperparathyroidism) includes the use of phosphorus binders and supplementation of active cellulose D, but the treatment rate is low. Cinacalcet hydrochloride is the first drug in a new class of calcimimetics, which can directly inhibit the secretion of parathyroid hormone (PTH) by activating the calcium receptor on parathyroid cells, and It has the effect of treating primary and secondary hyperparathyroidism. In addition, it is used for the treatment of secondary hyperparathyroidism in patients with kidney disease and dialysis, and has a g...

Claims

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Application Information

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IPC IPC(8): C07C211/30C07C209/60C07C209/50
Inventor 傅尧付明臣尚睿成万民
Owner UNIV OF SCI & TECH OF CHINA
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