A kind of method of synthesizing butenafine

A technology of butenafine and its compound, which is applied in the field of pharmaceutical chemical synthesis, can solve the problems of high synthesis cost, complicated operation, and easy oxidation, and achieve the effects of simple synthesis method, wide source of raw materials, and avoidance of residues

Inactive Publication Date: 2017-03-01
UNIV OF SCI & TECH OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0009] However, in these methods, the whole process of the above-mentioned route 1 is complicated to operate, and is accompanied by a large amount of inorganic salt by-products to generate
Moreover, the conversion process of Route 2 above requires high pressure [CO 2 / H 2 (20 / 60bar)], it is not easy to operate, and 1-naphthaldehyde is unstable and easily oxidized
In addition, the noble metal ruthenium is used for catalysis, and the ruthenium catalyst is expensive, which not only makes the synthesis cost higher, but also causes the metal to remain in the synthesized drug due to the participation of the metal catalyst, resulting in the unsafe problem of the obtained drug At the same time, the use of precious metals will also make the whole synthesis process not environmentally friendly, which does not meet the requirements of today's green chemistry

Method used

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  • A kind of method of synthesizing butenafine
  • A kind of method of synthesizing butenafine
  • A kind of method of synthesizing butenafine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] (1) The compound of formula I, i.e. the preparation of N-(4-(tert-butyl)benzyl)-1-naphthylcarboxamide

[0062] Add 20 mL of CH to a 100 mL round bottom flask 2 Cl 2 and 5mmol 4-tert-butylbenzylamine, dissolved. Then 20 mmol of triethylamine was added, and the mixture was stirred at 20° C. (using an IKA magnetic stirrer, RCT basic type, stirring speed 500 rpm). 7.5 mmol of 1-naphthoyl chloride was slowly added dropwise. After reacting for 10 h, add 30 mL of saturated NaHCO 3 solution, extracted with ether (20mL x 3), the organic phase was dried with anhydrous sodium sulfate, filtered, the organic phase was concentrated by a rotary evaporator (Buchi Co., Ltd., Switzerland, BUCHI rotary evaporator R-3), and then passed through a chromatography column ( Beijing Xinweier Glass Instrument Co., Ltd., C383040C chromatography column with sand plate storage ball, 35 / 20, φ30mm, effective length: 500ml) was separated by chromatography to obtain light yellow crystal product N-(4...

Embodiment 2

[0069] (1) The compound of formula I, i.e. the preparation of N-(4-(tert-butyl)benzyl)-1-naphthylcarboxamide

[0070] Carry out with the procedure same as Example 1, just change 5mmol 1-naphthoyl chloride into 5.0mmol 1-naphthoyl chloride, after reacting at 20 ℃ for 10h, obtain light yellow crystal product N-( 4-(tert-butyl)benzyl)-1-naphthylcarboxamide, yield 75%.

[0071] (2) the target product of formula II, i.e. the preparation of N-methyl-N-(naphthalene-1-ylmethyl)-1-(4-tert-butylphenyl) methylamine

[0072] The same procedure as in Example 1 was followed, except that the reaction mixture was heated at 100° 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 85%.

[0073] Gained product is carried out proton nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum analysis and confirms that gained product is N-methyl-N-(naphthalene-1-ylmethyl)-1-(4-tert-butylphenyl...

Embodiment 3

[0075] (1) The compound of formula I, i.e. the preparation of N-(4-(tert-butyl)benzyl)-1-naphthylcarboxamide

[0076] With embodiment 1.

[0077] (2) the target product of formula II, i.e. the preparation of N-methyl-N-(naphthalene-1-ylmethyl)-1-(4-tert-butylphenyl) methylamine

[0078] The same procedure as in Example 1 was carried out 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 92%.

[0079] Gained product is carried out proton nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum analysis, confirms that gained product is N-methyl-N-(naphthalene-1-ylmethyl)-1-(4-tert-butylphenyl) methylamine, That is butenafine.

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Abstract

The present invention discloses a butenafine synthesis method, the butenafine is shown as formula II, a desired product is prepared from 4-tert-butyl-benzylamine, 1-naphthoyl chloride, and formic acid as starting materials by amidation and reductive methylation two-step method by use of a non-metallic boron compound as a catalyst and an organic silane compound as a reducing agent, the butenafine synthesis method is simple, easy to operate, wide in source of raw materials, and low in cost; and a metal catalyst is not required to participate in the synthesis, the metal residues in the medicine can be avoided, and the method is safe, environmentally-friendly, and in line with 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 Butenafine. Background technique [0002] The chemical name of butenafine is: N-methyl-N-(naphthalene-1-ylmethyl)-1-(4-tert-butylphenyl) methylamine, and its structure is represented by the following formula (II): [0003] [0004] Butenafine was developed by Penederm Company in 1992. Its trade name is Mentax Cream. It is currently on the market in China, Japan, the United States and other countries. It belongs to allylamines together with Naftifine (Naftifine) and Terbinafine (Terbinafine). Antifungal drug, which blocks the synthesis of fungal cell membrane ergosterol by inhibiting squalene cyclooxygenase, and is mainly used for the treatment of skin fungal infections such as tinea corporis, jock itch, tinea pedis and tinea versicolor, and its curative effect is obviously better than that of gram Miconazole, miconazole, bifonazole an...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C211/27C07C209/50
Inventor 傅尧付明臣尚睿成万民
Owner UNIV OF SCI & TECH OF CHINA
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