JPH09255643A - New n-benzylbenzamide derivative - Google Patents
New n-benzylbenzamide derivativeInfo
- Publication number
- JPH09255643A JPH09255643A JP9757296A JP9757296A JPH09255643A JP H09255643 A JPH09255643 A JP H09255643A JP 9757296 A JP9757296 A JP 9757296A JP 9757296 A JP9757296 A JP 9757296A JP H09255643 A JPH09255643 A JP H09255643A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- general formula
- derivative
- methyl
- benzylbenzamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- LKQUCICFTHBFAL-UHFFFAOYSA-N n-benzylbenzamide Chemical class C=1C=CC=CC=1C(=O)NCC1=CC=CC=C1 LKQUCICFTHBFAL-UHFFFAOYSA-N 0.000 title claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 26
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 4
- DGYQJGIGKIABRU-UHFFFAOYSA-N 4-tert-butyl-n-methyl-n-[(2-phenylphenyl)methyl]benzamide Chemical compound C=1C=C(C(C)(C)C)C=CC=1C(=O)N(C)CC1=CC=CC=C1C1=CC=CC=C1 DGYQJGIGKIABRU-UHFFFAOYSA-N 0.000 claims abstract description 3
- -1 N- (4-tert-butylbenzyl) -N-methyl-4-phenylbenzoic acid amide Chemical compound 0.000 claims description 5
- 229940125904 compound 1 Drugs 0.000 claims description 5
- 229940125782 compound 2 Drugs 0.000 claims description 5
- 229940126214 compound 3 Drugs 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- GRTYNCJDHCGUDA-UHFFFAOYSA-N n-benzhydryl-4-tert-butyl-n-methylbenzamide Chemical compound C=1C=C(C(C)(C)C)C=CC=1C(=O)N(C)C(C=1C=CC=CC=1)C1=CC=CC=C1 GRTYNCJDHCGUDA-UHFFFAOYSA-N 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 239000003429 antifungal agent Substances 0.000 abstract description 11
- 229940121375 antifungal agent Drugs 0.000 abstract description 11
- 239000002994 raw material Substances 0.000 abstract description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 6
- 239000002904 solvent Substances 0.000 abstract description 5
- IOHPVZBSOKLVMN-UHFFFAOYSA-N 2-(2-phenylethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CCC1=CC=CC=C1 IOHPVZBSOKLVMN-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003638 chemical reducing agent Substances 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 150000004820 halides Chemical class 0.000 abstract description 2
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical class CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 abstract description 2
- 238000010898 silica gel chromatography Methods 0.000 abstract description 2
- BWMISRWJRUSYEX-SZKNIZGXSA-N terbinafine hydrochloride Chemical compound Cl.C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 BWMISRWJRUSYEX-SZKNIZGXSA-N 0.000 abstract description 2
- 229940124597 therapeutic agent Drugs 0.000 abstract description 2
- 201000004647 tinea pedis Diseases 0.000 abstract description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 230000000843 anti-fungal effect Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- QUAFTMJUVQDZHE-UHFFFAOYSA-N 3-(4-chloroanilino)-6-hydroxy-9-methylcarbazole-1,4-dione Chemical compound ClC1=CC=C(C=C1)NC1=CC(C=2N(C3=CC=C(C=C3C=2C1=O)O)C)=O QUAFTMJUVQDZHE-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DUZCVTGQWLHTOG-UHFFFAOYSA-N 1-(4-tert-butylphenyl)-n-methyl-n-[(2-phenylphenyl)methyl]methanamine Chemical compound C=1C=CC=C(C=2C=CC=CC=2)C=1CN(C)CC1=CC=C(C(C)(C)C)C=C1 DUZCVTGQWLHTOG-UHFFFAOYSA-N 0.000 description 1
- VGVNBMKGSXHVTB-UHFFFAOYSA-N 1-(4-tert-butylphenyl)-n-methyl-n-[(3-phenylphenyl)methyl]methanamine Chemical compound C=1C=CC(C=2C=CC=CC=2)=CC=1CN(C)CC1=CC=C(C(C)(C)C)C=C1 VGVNBMKGSXHVTB-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- ILYSAKHOYBPSPC-UHFFFAOYSA-N 2-phenylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=CC=C1 ILYSAKHOYBPSPC-UHFFFAOYSA-N 0.000 description 1
- NNJMFJSKMRYHSR-UHFFFAOYSA-N 4-phenylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 NNJMFJSKMRYHSR-UHFFFAOYSA-N 0.000 description 1
- KDVYCTOWXSLNNI-UHFFFAOYSA-N 4-t-Butylbenzoic acid Chemical compound CC(C)(C)C1=CC=C(C(O)=O)C=C1 KDVYCTOWXSLNNI-UHFFFAOYSA-N 0.000 description 1
- PPDDOKJBEAPPTJ-UHFFFAOYSA-N CC(C)(C)C1=CC=C(C=C1)C(=O)NCC2=CC=CC=C2C3=CC=CC=C3 Chemical compound CC(C)(C)C1=CC=C(C=C1)C(=O)NCC2=CC=CC=C2C3=CC=CC=C3 PPDDOKJBEAPPTJ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000223238 Trichophyton Species 0.000 description 1
- ZDVDCDLBOLSVGM-UHFFFAOYSA-N [chloro(phenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(Cl)C1=CC=CC=C1 ZDVDCDLBOLSVGM-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical class NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- XRRHTQGYPDJPCH-UHFFFAOYSA-N n-[(4-tert-butylphenyl)methyl]-n-methyl-1-(4-phenylphenyl)methanamine Chemical compound C=1C=C(C(C)(C)C)C=CC=1CN(C)CC(C=C1)=CC=C1C1=CC=CC=C1 XRRHTQGYPDJPCH-UHFFFAOYSA-N 0.000 description 1
- FXXBKXHFEBSUHS-UHFFFAOYSA-N n-methyl-1-(2-phenylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1C1=CC=CC=C1 FXXBKXHFEBSUHS-UHFFFAOYSA-N 0.000 description 1
- UERSZVOVPLBEHC-UHFFFAOYSA-N n-methyl-2-phenylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1C1=CC=CC=C1 UERSZVOVPLBEHC-UHFFFAOYSA-N 0.000 description 1
- NCCHARWOCKOHIH-UHFFFAOYSA-N n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1 NCCHARWOCKOHIH-UHFFFAOYSA-N 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 201000009862 superficial mycosis Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は抗真菌剤の合成原料
として有用な、新規Ｎ−ベンジルベンズアミド誘導体に
関する。TECHNICAL FIELD The present invention relates to a novel N-benzylbenzamide derivative useful as a raw material for the synthesis of antifungal agents.
【０００２】[0002]
【従来の技術】水虫に代表される表在性真菌症は、生活
が西洋化して靴の着用時間が増加したのに相まって、未
だに確実な治療法及び治療薬が見いだされていないこと
もあり、現代に於ける克服されていない疾病の一つに数
えられている。その為、抗真菌作用について、多くの化
合物がスクリーニングにかけられた。しかしながら、ｉ
ｎ ｖｉｔｒｏ或いは動物レベルに於いて活性が見いだ
された物質でも、実際の臨床段階においてはドロップア
ウトするものが少なくなく、満足いく結果は今のところ
得られたものは極めて少ない。即ち、新規の抗真菌作用
を有する母核の発見が待たれていた。この様な状況下本
発明者等は一般式（ＩＩ）に示される化合物が優れた抗
真菌作用を有することを見いだした。例えば、一般式
（ＩＩ）に表される化合物の内、４−ターシャリーブチ
ル−Ｎ−メチル−Ｎ−（２−フェニルベンジル）ベンジ
ルアミン（抗真菌剤１）、４−ターシャリーブチル−Ｎ
−メチル−Ｎ−（３−フェニルベンジル）ベンジルアミ
ン（抗真菌剤２）、４−ターシャリーブチル−Ｎ−メチ
ル−Ｎ−（４−フェニルベンジル）ベンジルアミン（抗
真菌剤３）、４−ターシャリーブチル−Ｎ−ジフェニル
メチル−Ｎ−メチルベンジルアミン（抗真菌剤４）は、
表１に示す様にトリコフィトン・メンタグラファイトに
対して優れた抗真菌作用を示す。一般式（ＩＩ）に表さ
れる化合物は新規化合物であり、従ってその製造方法は
知られていない。又、本発明の化合物である、一般式
（Ｉ）に表される化合物も文献未記載の新規化合物であ
る。2. Description of the Related Art Superficial mycosis represented by athlete's foot is that, due to the westernization of life and the increase in wearing time of shoes, there is still a case where a definite therapeutic method and a therapeutic agent have not been found yet. It is counted as one of the diseases that have not been overcome in modern times. Therefore, many compounds were screened for antifungal activity. However, i
Of the substances found to be active at the level of n vitro or at the animal level, many drop out in the actual clinical stage, and very few satisfactory results have been obtained so far. That is, the discovery of a mother nucleus having a novel antifungal action has been awaited. Under such circumstances, the present inventors have found that the compound represented by the general formula (II) has an excellent antifungal action. For example, among the compounds represented by the general formula (II), 4-tert-butyl-N-methyl-N- (2-phenylbenzyl) benzylamine (antifungal agent 1), 4-tert-butyl-N
-Methyl-N- (3-phenylbenzyl) benzylamine (antifungal agent 2), 4-tertiarybutyl-N-methyl-N- (4-phenylbenzyl) benzylamine (antifungal agent 3), 4-tersia Libutyl-N-diphenylmethyl-N-methylbenzylamine (antifungal agent 4) is
As shown in Table 1, it exhibits an excellent antifungal action against Trichophyton menthagraphite. The compound represented by the general formula (II) is a novel compound, and therefore its production method is unknown. Further, the compound represented by the general formula (I), which is the compound of the present invention, is a novel compound not described in the literature.
【０００３】[0003]
【化５】 一般式（ＩＩ） （但し、式中Ｒ１、Ｒ４はそれぞれ独立に水素原子又は
置換基を有していても良い炭素数６〜１８の芳香族炭化
水素を表し、Ｒ２、Ｒ３はそれぞれ独立に炭素数１〜４
のアルキル基を表し、ｍ、ｎはそれぞれ独立に１〜４の
整数を表す。）Embedded image General formula (II) (In the formula, R1 and R4 each independently represent a hydrogen atom or an aromatic hydrocarbon having 6 to 18 carbon atoms which may have a substituent, and R2 and R3 each independently represent a carbon atom. Number 1-4
Represents an alkyl group, and m and n each independently represent an integer of 1 to 4. )
【０００４】[0004]
【化６】 （抗真菌剤１）[Chemical 6] (Antifungal agent 1)
【０００５】[0005]
【化７】 （抗真菌剤２）Embedded image (Antifungal agent 2)
【０００６】[0006]
【化８】 （抗真菌剤３）Embedded image (Antifungal agent 3)
【０００７】[0007]
【化９】 （抗真菌剤４）Embedded image (Antifungal agent 4)
【０００８】[0008]
【表１】 [Table 1]
【０００９】[0009]
【発明が解決しようとする課題】本発明は、この様な状
況下為されたものであり、抗真菌剤である、一般式（Ｉ
Ｉ）の化合物を合成するのに有用な原料を提供すること
を課題とする。。SUMMARY OF THE INVENTION The present invention has been made under these circumstances and is an antifungal agent represented by the general formula (I
It is an object to provide a raw material useful for synthesizing the compound of I). .
【００１０】[0010]
【課題を解決するための手段】本発明者らは、この様な
状況に鑑み、一般式（ＩＩ）の合成原料の開発研究につ
いて鋭意努力を重ねた結果、一般式（Ｉ）に示す化合物
群が有用な原料になりうることを見いだし、発明を完成
させるに至った。以下、本発明について詳細に説明す
る。In view of such circumstances, the inventors of the present invention have made diligent efforts to research and develop synthetic raw materials of the general formula (II), and as a result, the compound group represented by the general formula (I) We have found that can be a useful raw material and have completed the invention. Hereinafter, the present invention will be described in detail.
【００１１】[0011]
【化１０】 一般式（Ｉ） （但し、式中Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｒ５、Ｒ６、Ｒ
７、Ｒ８はそれぞれ独立に、水素原子、炭素数１〜４の
アルキル基又はフェニル基を表し、且つ、これらの置換
の少なくとも１個はフェニル基であるものとする。）Embedded image General formula (I) (wherein R1, R2, R3, R4, R5, R6, R
7 and R8 each independently represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a phenyl group, and at least one of these substitutions is a phenyl group. )
【００１２】一般式（Ｉ）に示す化合物は、リチウムア
ルミニウムハイドライド等で還元することにより、一般
式（ＩＩ）の化合物へと導くことが出来る。一般式
（Ｉ）の化合物はアミンと酸クロライドの反応により、
市販の試薬より容易に得ることが出来る。従って、一般
式（Ｉ）の化合物は一般式（ＩＩ）の化合物の有用な合
成原料であるといえる。The compound represented by the general formula (I) can be converted into the compound represented by the general formula (II) by reducing with lithium aluminum hydride or the like. The compound of the general formula (I) is obtained by reacting an amine with an acid chloride,
It can be easily obtained from commercially available reagents. Therefore, it can be said that the compound of the general formula (I) is a useful synthetic raw material for the compound of the general formula (II).
【００１３】[0013]
【発明の実施の形態】本発明の化合物は、一般式（Ｉ）
に表されるＮ−ベンジルベンズアミド誘導体である。一
般式（Ｉ）に表される化合物は、次に示す反応式１に従
って合成できる。即ち、安息香酸誘導体から導いた、Ｎ
−メチルベンジルアミン誘導体に、対応するハロゲン化
物をトリエチルアミン等の塩基存在下反応させればよ
い。かくして得られた化合物は、例えば、シリカゲルカ
ラムクロマトグラフィーや再結晶などの通常の精製手段
で精製することが出来る。この様な一般式（Ｉ）に表さ
れる化合物としては、例えば、Ｎ−メチル−Ｎ−（２−
フェニルベンジル）−４−ターシャリーブチル安息香酸
アミド（化合物１）、Ｎ−（４−ターシャリーブチルベ
ンジル）−Ｎ−メチル−４−フェニル安息香酸アミド
（化合物２）、Ｎ−（ジフェニルメチル）−Ｎ−メチル
−４−ターシャリーブチル安息香酸アミド（化合物３）
等が好適に例示できる。これらの一般式（Ｉ）に表され
る化合物は、リチウムアルミニウムハイドライドの様な
還元剤をエーテル等の溶媒中で反応させることにより容
易に一般式（ＩＩ）に表される化合物へと導くことが可
能である。BEST MODE FOR CARRYING OUT THE INVENTION The compounds of the present invention have the general formula (I)
Is an N-benzylbenzamide derivative. The compound represented by the general formula (I) can be synthesized according to reaction formula 1 shown below. That is, N derived from a benzoic acid derivative
-The methylbenzylamine derivative may be reacted with the corresponding halide in the presence of a base such as triethylamine. The compound thus obtained can be purified by a conventional purification means such as silica gel column chromatography or recrystallization. Examples of such a compound represented by the general formula (I) include N-methyl-N- (2-
Phenylbenzyl) -4-tert-butylbenzoic acid amide (Compound 1), N- (4-tert-butylbenzyl) -N-methyl-4-phenylbenzoic acid amide (Compound 2), N- (diphenylmethyl)- N-methyl-4-tert-butylbenzoic acid amide (Compound 3)
And the like can be preferably exemplified. These compounds represented by the general formula (I) can be easily led to the compounds represented by the general formula (II) by reacting a reducing agent such as lithium aluminum hydride in a solvent such as ether. It is possible.
【００１４】[0014]
【化１１】 反応式１Embedded image Reaction formula 1
【００１５】[0015]
【化１２】 化合物１Embedded image Compound 1
【００１６】[0016]
【化１３】 化合物２Embedded image Compound 2
【００１７】[0017]
【化１４】 化合物３Embedded image Compound 3
【００１８】[0018]
実施例１ 製造例 クロロホルム１００ｍｌにｏ−フェニル安息香酸１０
ｇ、塩化チオニル１８．７ｇを混合し４時間加熱還流し
た。反応物を減圧濃縮し、これを氷冷下４０％メチルア
ミン水溶液４０ｍｌに滴下した。混合物を室温まで戻
し、４日間攪拌し反応させた。２Ｎ塩酸を加え反応を止
め、クロロホルムで抽出し有機層を飽和炭酸水素ナトリ
ウム溶液で洗浄した。有機層を取り溶媒を溜去し、Ｎ−
メチル−２−フェニル安息香酸アミドを得た。これをエ
ーテル中０．５４ｇのリチウムアルムニウムハイドライ
ドで還元し、１．４６ｇのＮ−メチル−２−フェニルベ
ンジルアミンを得た。これと１．４５ｇのｐ−ターシャ
リーブチル安息香酸から誘導した酸クロライドをベンゼ
ン中でトリエチルアミンの存在下反応させ、反応液に水
とクロロホルムを加え抽出し、有機層を取り、希塩酸、
飽和炭酸水素ナトリウム水溶液、水、飽和食塩水の順で
洗浄した。溶媒を溜去し黄色結晶として、Ｎ−メチル−
Ｎ−（２−フェニルベンジル）−４−ターシャリーブチ
ル安息香酸アミド（化合物１）を２．４２ｇ得た。ＮＭ
Ｒ（溶媒：重クロロホルム）は次の通りであった。 １Ｈ−δｐｐｍ；１．３１（９Ｈ，ｓ）、２．８１（３
Ｈ，ｄ）、４．６３（２Ｈ，ｄ）７．００〜７．４１
（１３Ｈ，ｍ）Example 1 Production Example o-Phenylbenzoic acid 10 was added to 100 ml of chloroform.
g and thionyl chloride 18.7 g were mixed and heated under reflux for 4 hours. The reaction product was concentrated under reduced pressure and added dropwise to 40 ml of a 40% methylamine aqueous solution under ice cooling. The mixture was returned to room temperature and stirred for 4 days to react. The reaction was stopped by adding 2N hydrochloric acid, extracted with chloroform, and the organic layer was washed with a saturated sodium hydrogen carbonate solution. The organic layer is taken and the solvent is distilled off, N-
Methyl-2-phenylbenzoic acid amide was obtained. This was reduced with 0.54 g of lithium aluminum hydride in ether to give 1.46 g of N-methyl-2-phenylbenzylamine. This was reacted with 1.45 g of an acid chloride derived from p-tert-butylbenzoic acid in benzene in the presence of triethylamine, and water and chloroform were added to the reaction solution for extraction. The organic layer was taken and diluted with hydrochloric acid,
It was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and saturated saline in this order. The solvent was distilled off to give N-methyl-yellow crystals.
2.42 g of N- (2-phenylbenzyl) -4-tert-butylbenzoic acid amide (Compound 1) was obtained. NM
R (solvent: deuterated chloroform) was as follows. 1H-δppm; 1.31 (9H, s), 2.81 (3
H, d), 4.63 (2H, d) 7.00-7.41
(13H, m)
【００１９】（例２）製造例 例１と同様にｐ−フェニル安息香酸２．４７ｇより、４
−ターシャリーブチル−Ｎ−メチル−Ｎ−（４−フェニ
ルベンジル）安息香酸アミド（化合物２）を白色結晶と
して１．５８ｇ得た。１Ｈ−ＮＭＲスペクトル（δｐｐ
ｍ、重クロロホルム）は次に示すとおり。 （ＮＭＲ） １．２６（９Ｈ，ｓ）、２．９９（３Ｈ，ｄ）、４．６
５（２Ｈ，ｄ）、７．１４〜７．５９（１３Ｈ，ｍ）(Example 2) Production Example Similar to Example 1, from 2.47 g of p-phenylbenzoic acid, 4
1.58 g of -tert-butyl-N-methyl-N- (4-phenylbenzyl) benzoic acid amide (Compound 2) was obtained as white crystals. 1H-NMR spectrum (δpp
m, deuterated chloroform) are as shown below. (NMR) 1.26 (9H, s), 2.99 (3H, d), 4.6
5 (2H, d), 7.14 to 7.59 (13H, m)
【００２０】（例３）製造例 例１と同様に、４．０６ｇのクロロジフェニルメタンよ
り、４−ターシャリーブチル−Ｎ−ジフェニルメチル−
Ｎ−メチル安息香酸アミド（化合物３）を白色結晶とし
て１．４８ｇ得た。（収率：４８．９％）１Ｈ−ＮＭＲ
スペクトル（δｐｐｍ、重クロロホルム）は次に示す通
り。 （ＮＭＲ） １．１６（９Ｈ，ｓ）、２．７２（３Ｈ，ｓ）、７．０
１〜７．２５（１４Ｈ，ｍ）(Example 3) Production Example As in Example 1, from 4.06 g of chlorodiphenylmethane, 4-tert-butyl-N-diphenylmethyl-
1.48 g of N-methylbenzoic acid amide (Compound 3) was obtained as white crystals. (Yield: 48.9%) 1H-NMR
The spectrum (δppm, deuterated chloroform) is as shown below. (NMR) 1.16 (9H, s), 2.72 (3H, s), 7.0
1 to 7.25 (14H, m)
【発明の効果】本発明によれば、抗真菌剤の原料として
好適な新規Ｎ−ベンジルアミド誘導体が提供できる。INDUSTRIAL APPLICABILITY According to the present invention, a novel N-benzylamide derivative suitable as a raw material for an antifungal agent can be provided.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 鈴木 利光 神奈川県横浜市戸塚区柏尾町560 ポーラ 化成工業株式会社戸塚研究所内 (72)発明者 馬島 敏郎 神奈川県横浜市戸塚区柏尾町560 ポーラ 化成工業株式会社戸塚研究所内 (72)発明者 湯浅 雅之 神奈川県横浜市戸塚区柏尾町560 ポーラ 化成工業株式会社戸塚研究所内 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Toshimitsu Suzuki 560 Kashio-cho, Totsuka-ku, Yokohama-shi, Kanagawa Pola Chemical Industry Co., Ltd.Totsuka Research Institute (72) Inventor Toshiro Majima 560, Kashio-cho, Totsuka-ku, Yokohama-shi, Kanagawa Pola Kasei Kogyo Totsuka Research Institute Co., Ltd. (72) Inventor Masayuki Yuasa 560 Kashio-cho, Totsuka-ku, Yokohama, Kanagawa Prefecture Pola Kasei Kogyo Co., Ltd.
Claims (2)
ンズアミド誘導体。 【化１】 一般式（Ｉ） （但し、式中Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｒ５、Ｒ６、Ｒ
７、Ｒ８はそれぞれ独立に、水素原子、炭素数１〜４の
アルキル基又はフェニル基を表し、且つ、これらの置換
の少なくとも１個はフェニル基であるものとする。）1. An N-benzylbenzamide derivative represented by the general formula (I). Embedded image General formula (I) (wherein R1, R2, R3, R4, R5, R6, R
7 and R8 each independently represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a phenyl group, and at least one of these substitutions is a phenyl group. )
メチル−Ｎ−（２−フェニルベンジル）−４−ターシャ
リーブチル安息香酸アミド（化合物１）、Ｎ−（４−タ
ーシャリーブチルベンジル）−Ｎ−メチル−４−フェニ
ル安息香酸アミド（化合物２）、Ｎ−（ジフェニルメチ
ル）−Ｎ−メチル−４−ターシャリーブチル安息香酸ア
ミド（化合物３）の何れかである請求項１記載のＮ−ベ
ンジルベンズアミド誘導体。 【化２】 化合物１ 【化３】 化合物２ 【化４】 化合物３2. The compound represented by the general formula (I) is N-
Methyl-N- (2-phenylbenzyl) -4-tert-butylbenzoic acid amide (Compound 1), N- (4-tert-butylbenzyl) -N-methyl-4-phenylbenzoic acid amide (Compound 2), The N-benzylbenzamide derivative according to claim 1, which is any one of N- (diphenylmethyl) -N-methyl-4-tert-butylbenzoic acid amide (Compound 3). Embedded image Compound 1 Compound 2 Compound 3
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP09757296A JP3866323B2 (en) | 1996-03-27 | 1996-03-27 | Novel N-benzylbenzamide derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP09757296A JP3866323B2 (en) | 1996-03-27 | 1996-03-27 | Novel N-benzylbenzamide derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH09255643A true JPH09255643A (en) | 1997-09-30 |
| JP3866323B2 JP3866323B2 (en) | 2007-01-10 |
Family
ID=14195962
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP09757296A Expired - Fee Related JP3866323B2 (en) | 1996-03-27 | 1996-03-27 | Novel N-benzylbenzamide derivatives |
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| Country | Link |
|---|---|
| JP (1) | JP3866323B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6015925A (en) * | 1998-09-17 | 2000-01-18 | Pola Chemical Industries, Inc. | Antifungal agents |
| JP2008514657A (en) * | 2004-09-29 | 2008-05-08 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | 4- {4-[({[4-Chloro-3- (trifluoromethyl) phenyl] amino} carbonyl) amino] phenoxy} -N-methylpyridine-2-carboxamide |
-
1996
- 1996-03-27 JP JP09757296A patent/JP3866323B2/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6015925A (en) * | 1998-09-17 | 2000-01-18 | Pola Chemical Industries, Inc. | Antifungal agents |
| JP2008514657A (en) * | 2004-09-29 | 2008-05-08 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | 4- {4-[({[4-Chloro-3- (trifluoromethyl) phenyl] amino} carbonyl) amino] phenoxy} -N-methylpyridine-2-carboxamide |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3866323B2 (en) | 2007-01-10 |
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