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Description: This patent application claims the benefit of priority under 35 U.S.C. §119 of German Patent Application No. 199 55 190.1, filed Nov. 16, 1999. German Patent Application No. 199 55 190.1 is incorporated herein in its entirety by reference. The present invention concerns highly pure, crystalline, stable compounds of novel derivatives of 3,3-diphenylpropylamines in the form of their salts, a method for manufacturing these and highly pure, stable, intermediate products. From document PCT/EP99/03212 novel derivatives of 3,3-diphenylproprylamines are known. These are valuable prodrugn for the treatment of urinary incontinence and other spasmodic complaints, which overcome the disadvantage of the active substances available to date, namely inadequate absorption of the active substance by biological membranes or the unfavourale metabolism of these. Furthermore these novel prodrugs have improved pharmacokinetic characteristics compared with Oxybutynin and Tolterodin. Preferred compounds from the group of these novel derivatives of 3,3-diphenylpropylarines are esters of aliphatic or aromatic carboxylic acids with the general formula A referred to below in which R denotes C 1 -C 6 -alkyl, C 3 -C 10 -cycloalkyl or unsubstituted or substituted phenyl. These can occur in their optical isomers form as racemic mixtures and in the form of their individual enantiomers. Compounds with the structure of formula A do, however, have low solubility in water. This restricts their oral bioavailability. Finally, monoesters of the structure, as shown in formula A, have a tendency towards intermolecular transesterification. During long periods of storage, therefore, as the content of the compounds with the structure of general formula A drops an increase in diesters and free diol can be detected. Basically salts of the compounds of general formula A can be obtained if solutions of the compounds of formula A (base component) are purified with solutions of acids in suitable solvents, but the salts obtained in the form of solid matter can prove to be altogether amorphous and/or hygroscopic and cannot be directly crystallized from the normal solvents either. Such salts have inadequate chemical stability to be galenically processed as valuable pharmaceutically active substances. Surprisingly, it has now been found that the abovementioned disadvantages can be avoided if compounds with the structure of general formula A, once they have been prepared under a special reaction process, are converted with a physiologically compatible inorganic or organic acid with general formula H-X, in which − X represents the respective acid residue, into their respective salt with general formula I. The problem for the present invention is therefore to provide highly pure, crystalline, stable compounds of novel derivatives of 3,3-diphenylpropylamines in the form of their salts, that avoid the stated disadvantages and are well suited to use in pharmaceutical-technical formulations and can be processed into these. A further problem for the present invention is to provide a method for manufacturing such highly pure, crystalline, stable compounds in the form of their salts, as well as highly pure, stable intermediate products. The final problem for the invention is to provide a method for manufacturing the abovementioned compounds with which a high yield of the products of the process and the respective intermediate products can be obtained chemo- or regioselectively. This problem is solved in that highly pure, crystalline, stable compounds of the 3,3-diphenylpropylamines in the form of their salts with general formula I are provided, in which R denotes C 1 -C 6 -alkyl, C 3 -C 10 -cycloalkyl, substituted or unsubstituted phenyl and X − is the acid residue of a physiologically compatible inorganic or organic acid. In accordance with a design of the invention the salts of general formula I can contain the respective acid residue X − of the acids mentioned below: • o hydrochloric acid, hydrobromic acid, phosphoric acid, sulphuric acid, nitric acid, acetic acid, propionic acid, palmitic acid, stearic acid, maleic acid, fumaric acid, oxalic acid, succinic acid, DL-malic acid, L-(−  -malic acid, D-(+)-malic acid, DL-tartaric acid, L-(+)-tartaric acid, D-(−-tartaric acid, citric acid, L-aspartic acid, L-(+)-ascorbic acid, D-(+)-glucuronic acid, 2-oxopropionic acid (pyruvic acid), furan-2-carboxylic acid (mucic acid), benzoic acid, 4-hydroxybenzoic acid, salicyclic acid, vanillic acid, 4-hydroxycinammic acid, gallic acid, hippuric acid (N-benzoyl-glycine), aceturic acid (N-aectylglycine), phloretinic acid (3-(4-hydroxyphenyl)-propionic acid), phthalic acid, methanesulfonic acid or orotic acid. In accordance with a further design form of the invention R-configured compounds with general formula 2 are provided in which R denotes C 1 -C 6 -alkyl, C 3 -C 10 -cycloalkyl, substituted or unsubstituted phenyl and X − is the acid residue of a physiologically compatible inorganic or organic acid. In accordance with an advantageous design form of the invention the compounds in the form of their salts of general formula 2 can contain the respective acid residue X − of the acids mentioned below: • o hydrochloric acid, hydrobromic acid, phosphoric acid, sulphuric acid, nitric acid, acetic acid, propionic acid, palmitic acid, stearic acid, maleic acid, fumaric acid, oxalic acid, succinic acid, DL-malic acid, L-(− -malic acid, D-(+)-malic acid, DL-tartaric acid, L-(+)-tartaric acid, D-(−-tartaric acid, citric acid, L-aspartic acid, L-(+)-ascorbic acid, D-(+)-glucuronic acid, 2-oxopropionic acid (pyruvic acid), furan-2-carboxylic acid (mucic acid), benzoic acid, 4-hydroxybenzoic acid, salicyclic acid, vanillic acid, 4-hydroxycinammic acid, gallic acid, hippuric acid (N-benzoyl-glycine), aceturic acid (N-aectylglycine), phloretinic acid (3-(4-hydroxyphenyl)-propionic acid), phthalic acid, methanesulfonic acid or orotic acid. Preferred compounds of the present invention are the salts • o R-(+)-2-(3-diisopropylamino-1-phenylpropyl)-4-hy droxymethylphenylisobutyrate ester hydrogen fumarate and o R-(+)-2-(3-diisopropylamino-1-phenylpropyl)-4-hy droxymethylphenylisobutyrate ester hydrochloride hydrate. Furthermore, compounds are preferred in which R stands for cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-(1-cyclo-propyl-methanoyloxy)-phenyl, 4-(1-cyclobutyl-methanoyloxy)-phenyl, 4-(1-cyclohexyl-methanoyloxy)-phenyl or 4-(2,2-dimethyl-propanoyloxy)-phenyl and X denotes chloride. Particular preference is for [(R)-3-(2-{1-[4-(1-cyclopropyl-methanoyloxy)-phenyl]-methano yloxy}-5-hydroxymethyl-phenyl)-3-phenyl-propyl]-diisopropyl- ammonium chloride, [(R)-3-(2-{1-[4-(1-cyclobutyl-methanoyloxy)-phenyl]-methanoy loxy}-5-hydroxymethyl-phenyl)-3-phenyl-propyl]-diisopropyl-a mmonium chloride, [(R)-3-(2-{1-[4-(1-cyclohexyl-methanoyloxy)-phenyl]-methanoy loxy}-5-hydroxymethyl-phenyl)-3-phenyl-propyl]-diisopropyl-a mmonium chloride, [(R)-3-(2-{1-[4-(2,2-dimethyl-propanoyloxy)-phenyl]-methanoy loxy}-5-hydroxymethyl-phenyl)-3-phenyl-propyl]-diisopropyl-a mmonium chloride, {(R)-3-[2-(1-cyclopropyl-methanoyloxy)-5-hydroxymethyl-pheny l]-3-phenyl-propyl}-diisopropyl-ammonium chloride, {(R)-3-[2-(1-cyclobutyl-methanoyloxy)-5-hydroxymethyl-phenyl ]-3-phenyl-propyl}-diisopropyl-ammonium chloride, {(R)-3-[2-(1-cyclopentyl-methanoyloxy)-5-hydroxymethyl-pheny l]-3-phenyl-propyl}-diisopropyl-ammonium chloride and {(R)-3-[2-(1-cyclohexyl-methanoyloxy)-5-hydroxymethyl-phenyl ]-3-phenyl-propyl}-diisopropyl-ammonium chloride. In the compounds of the present invention the expression “alkyl” preferably stands for a straight-chain or branched-chain hydrogen group with between 1 and 6 C-atoms. Special preference is for methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl and hexyl. The expression “cycloalkyl” designates cyclical hydrogen groups, that have between 3 and 10 hydrogen atoms, that may also contain suitable substitutes in place of the hydrogen atoms. The expression “phenyl” designates a —C 6 H 5 -group that may be substituted or unsubstituted. Suitable substitutes can be, for example, alkyl, alkoxy, halogen, nitro and amine. The expression “alkoxy” has, with respect to the alkyl component, the same meaning as already given above for “alkyl”. Suitable halogens are fluorine, chlorine, bromine and iodine atoms The present invention also includes methods for manufacturing the compounds in accordance with the invention of general formula I as well as valuable intermediate products. The method is characterised by chemo- and regioselectivity. Compounds of General Formula I in which R denotes C 1 -C 6 -alkyl, C 3 -C 10 -cycloalkyl, substituted or unsubstituted phenyl and X − is the acid residue of a physiologically compatible inorganic or organic acid, are that • o a) a compound of formula III is split with a hydrogenation agent to form a compound of formula V whereupon o b) the compound of formula V so obtained is converted with agent, in order to give a compound of formula VI which o c) is converted with an acylation agent, in order to obtain of formula A in which R has the significance stated above, which d) is converted with a physiologically compatible inorganic or organic acid to form a compound of formula I in which R denotes C 1 -C 6 -alkyl, C 3 -C 10 -cycloalkyl, unsubstituted or substituted phenyl and X− is the acid residue of a physiologically compatible inorganic or organic acid. In accordance with the invention, for the manufacture of the compounds of general formula I hydrochloric acid, hydrobromic acid, phosphoric acid, sulphuric acid, nitric acid, acetic acid, propionic acid, palmitic acid, stearic acid, maleic acid, fumaric acid, oxalic acid, succinic acid, DL-malic acid, L-(− -malic acid, D-(+)-malic acid, DL-tartaric acid, L-(+)-tartaric acid, D-(−-tartaric acid, citric acid, L-aspartic acid, L-(+)-ascorbic acid, D-(+)-glucuronic acid, 2-oxopropionic acid (pyruvic acid), furan-2-carboxylic acid (mucic acid), benzoic acid, 4-hydroxybenzoic acid, salicyclic acid, vanillic acid, 4-hydroxycinammic acid, gallic acid, hippuric acid (N-benzoyl-glycine), aceturic acid (N-aectylglycine), phloretinic acid (3-(4-hydroxyphenyl)-propionic acid), phthalic acid, methanesulfonic acid or orotic acid are used. In accordance with an advantageous further development of the invention a method for the manufacture of R-configured compounds of the general formula 2 is described, in which R denotes C 1 -C 6 -alkyl, C 3 -C 10 -cycloalkyl, substituted or unsubstituted phenyl and X − is the acid residue of a physiologically compatible inorganic or organic acid, in that • o a) a compound of formula 3 is split with a hydrogenation agent to form a compound of formula 5 whereupon o b) the compound of formula 5 so obtained is converted with a reducing agent, in order to give a compound of formula 6 which o c) is converted with an acylation agent, in order to obtain a compound of formula 1 in which R has the significance stated above, which o d) is converted with a physiologically compatible inorganic or organic acid to form a compound of formula 2 in which R denotes C 1 -C 6 -alkyl, C 3 -C 10 -cycloalkyl, unsubstituted or substituted phenyl and X− is the acid residue of a physiologically compatible inorganic or organic acid. Advantageously in order to obtain compounds of general formula 2, in accordance with the method hydrochloric acid, hydrobromic acid, phosphoric acid, sulphuric acid, nitric acid, acetic acid, propionic acid, palmitic acid, stearic acid, maleic acid, fumaric acid, oxalic acid, succinic acid, DL-malic acid, L-(− -malic acid, D-(+)-malic acid, DL-tartaric acid, L-(+)-tartaric acid, D-(−-tartaric acid, citric acid, L-aspartic acid, L-(+)-ascorbic acid, D-(+) -glucuronic acid, 2-oxopropionic acid (pyruvic acid), furan-2-carboxylic acid (mucic acid), benzoic acid, 4-hydroxybenzoic acid, salicyclic acid, vanillic acid, 4-hydroxycinammic acid, gallic acid, hippuric acid (N-benzoyl-glycine), aceturic acid (N-aectylglycine), phloretinic acid (3-(4-hydroxyphenyl)-propionic acid), phthalic acid, methanesulfonic acid or orotic acid are used. Particular advantageously, on the basis of the crystalline R-(− -4-benzyloxy-3-(3-diisopropylamino-1-phenyl-propyl)be nzoic acid methyl ester, the highly pure, crystalline intermediate product R-(−-3-(3-diisopropylamino-phenyl-propyl)-4-hydroxy-benzo ic acid methyl ester is prepared, which is reduced to R-(+)-2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethylp henol, is finally acylated in a suitable manner and is then converted with a physiologically compatible inorganic or organic acid under spontaneous crystallization to the respective highly pure, crystalline, stable salt. Depending on the acid chloride used, compounds of general formula 1 are obtained, in which R denotes C 1 -C 6 -alkyl, in particular isopropyl, C 3 -C 10 -cycloalkyl or unsubstituted or substituted phenyl. |
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davidyanli
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wypward(金幣+3):這是谷歌翻譯的吧！但還是謝謝參與 2010-05-24 09:22:36
wypward(金幣+3):這是谷歌翻譯的吧！但還是謝謝參與 2010-05-24 09:22:36
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描述: 該專利申請(qǐng)要求優(yōu)先權(quán)的35歲以下的編119德國(guó)中華民國(guó)專利申請(qǐng)案號(hào)(55 190.1、歸檔。199年11月16日。德國(guó)的專利申請(qǐng)?zhí)?90.1 199 55一同被整合,以供參考。 本發(fā)明關(guān)切的高純度、水晶、穩(wěn)定的混合物,3-diphenylpropylamines小說的衍生3的形式的一種方法,他們的鹽、高純度,生產(chǎn)這些、穩(wěn)定、中間產(chǎn)品。 從文件EP99/03212 PCT / 3,3-diphenylproprylamines衍生物的小說是眾所周知的。 這些都是珍貴的prodrugn治療性尿失禁和其他船上投訴,克服不利的活性物質(zhì)可到目前為止,即不足的活性物質(zhì)的吸收由生物膜或unfavourale代謝。 而且這些小說已經(jīng)改善代謝特點(diǎn)熱點(diǎn)和Tolterodin Oxybutynin相比。 優(yōu)先化合物的這些小說中有3個(gè),3-diphenylpropylarines衍生的脂肪或芳香羧酸酯酸與一般公式是指以下 在R代表C 1 -C 6 -alkyl、C 3 -C 10 -cycloalkyl或unsubstituted或取代苯。這些可以發(fā)生在他們的光學(xué)異構(gòu)體用表格的形式混合物和個(gè)人對(duì)映體。 化合物的結(jié)構(gòu),然而,一個(gè)做公式水溶性較低。這種限制他們的口腔生物利用度。 最后,使結(jié)構(gòu),如圖配方,有一間以傾向。在長(zhǎng)期貯存,因此,為內(nèi)容的化合物的結(jié)構(gòu),增加的一般表達(dá)式,在其中一個(gè)滴醇能被探測(cè)到,免費(fèi)。 基本上鹽的通用公式的化合物是可以解決的公式的化合物(組件基)的純化解酸在適當(dāng)?shù)娜軇?但是鹽的形式獲得固體物質(zhì)不能證明是共晶和/或吸濕性,不能直接從正常的溶劑結(jié)晶。這樣的鹽不足的化學(xué)穩(wěn)定性是galenically處理為價(jià)值”活性物質(zhì)。 令人驚訝的是,它現(xiàn)在已經(jīng)發(fā)現(xiàn)上述缺點(diǎn)可以避免的化合物的結(jié)構(gòu)一般公式,一旦他們已經(jīng)準(zhǔn)備下一個(gè)特別的反應(yīng)過程,為有生理兼容的無機(jī)或有機(jī)酸和一般公式,H-X−X代表各自的酸性渣,為各自的鹽與一般的公式。 本發(fā)明的問題,因此提供的高純度、水晶、穩(wěn)定的混合物,3-diphenylpropylamines小說的衍生3的形式,避免了他們的鹽陳述弊端,非常適合用于pharmaceutical-technical配方,可加工成這些。 進(jìn)一步的問題,本發(fā)明提供一種高純度為制造這樣,水晶,穩(wěn)定化合物的形式的鹽,以及高純度、穩(wěn)定的中間體。 最后的問題是提供了一種方法發(fā)明制造上述化合物和高產(chǎn)的產(chǎn)品的工藝及各自的中間產(chǎn)品可以獲得——或者可以化療。 這個(gè)問題已經(jīng)解決,高純度、水晶、穩(wěn)定化合物的三、3-diphenylpropylamines的鹽的形式與一般公式我, 在R代表C 1 -C 6 -alkyl、C 3 -C 10 -cycloalkyl取代苯、unsubstituted,或者是酸性渣X−的生理兼容的無機(jī)或有機(jī)酸。 按照設(shè)計(jì)的一般公式,發(fā)明了鹽,我可以包含了各自的酸性渣X−以下的氨基酸。 • 啊,hydrobromic鹽酸酸、磷酸、硫酸、硝酸、醋酸、丙酸、酸、硬脂酸、馬來酸、富馬酸、草酸琥珀酸、DL-malic酸、L -(−-malic酸、D -(+)-malic酸、DL-tartaric酸、L -(+)-tartaric酸、D -(−-tartaric酸、檸檬酸、天冬氨酸、L -(+)-ascorbic酸、D -(+)-glucuronic酸、2-oxopropionic酸(丙酮酸),furan-2-carboxylic酸(mucic酸)、苯甲酸、4-hydroxybenzoic酸、salicyclic酸、vanillic酸、4-hydroxycinammic酸、沒食子酸、馬尿酸(N-benzoyl-glycine),aceturic酸(N-aectylglycine),phloretinic酸(3 -(4-hydroxyphenyl)-propionic酸)、鄰苯二甲酸、四種羧酸或orotic酸。 依照進(jìn)一步設(shè)計(jì)的一般公式R-configured發(fā)明和2個(gè)被提供 在R代表C 1 -C 6 -alkyl、C 3 -C 10 -cycloalkyl取代苯、unsubstituted,或者是酸性渣X−的生理兼容的無機(jī)或有機(jī)酸。 依照一個(gè)有利的設(shè)計(jì)形式的發(fā)明的形式的化合物的一般公式的鹽可容納2×−各自的酸性渣酸下面提到: • 啊,hydrobromic鹽酸酸、磷酸、硫酸、硝酸、醋酸、丙酸、酸、硬脂酸、馬來酸、富馬酸、草酸琥珀酸、DL-malic酸、L -(−-malic酸、D -(+)-malic酸、DL-tartaric酸、L -(+)-tartaric酸、D -(−-tartaric酸、檸檬酸、天冬氨酸、L -(+)-ascorbic酸、D -(+)-glucuronic酸、2-oxopropionic酸(丙酮酸),furan-2-carboxylic酸(mucic酸)、苯甲酸、4-hydroxybenzoic酸、salicyclic酸、vanillic酸、4-hydroxycinammic酸、沒食子酸、馬尿酸(N-benzoyl-glycine),aceturic酸(N-aectylglycine),phloretinic酸(3 -(4-hydroxyphenyl)-propionic酸)、鄰苯二甲酸、四種羧酸或orotic酸。 本發(fā)明的優(yōu)先化合物的鹽 • o R -(+)- 2 -(3-diisopropylamino-1-phenylpropyl)-4-hy droxymethylphenylisobutyrate富氫酯和 o R -(+)- 2 -(3-diisopropylamino-1-phenylpropyl)-4-hy droxymethylphenylisobutyrate酯鹽酸鹽保濕。 再者,化合物的首選,cyclobutyl R代表cyclopropyl,cyclopentyl,cyclohexyl、4 -(2)-phenyl 1-cyclo-propyl-methanoyloxy,4 -(2)-phenyl 1-cyclobutyl-methanoyloxy,4 -(2)-phenyl 1-cyclohexyl-methanoyloxy或4 -(2)-phenyl 2-dimethyl-propanoyloxy和X表示。 特別偏愛是[(R)- 3 -(2 - { 1 - 4 -(1-cyclopropyl-methanoyloxy)-phenyl]-methano yloxy } -5-hydroxymethyl-phenyl)-3-phenyl-propyl]-diisopropyl -氯化銨,[(R)- 3 -(2 - { 1 - 4 -(1-cyclobutyl-methanoyloxy)-phenyl]-methanoy loxy } -5-hydroxymethyl-phenyl)-3-phenyl-propyl]-diisopropyl-a mmonium氯、[(R)- 3 -(2 - { 1 - 4 -(1-cyclohexyl-methanoyloxy)-phenyl]-methanoy loxy } -5-hydroxymethyl-phenyl)-3-phenyl-propyl]-diisopropyl-a mmonium氯、[(R)- 3 -(2 - { 1 - 4 -(2)-phenyl]-methanoy 2-dimethyl-propanoyloxy loxy } -5-hydroxymethyl-phenyl)-3-phenyl-propyl]-diisopropyl-a mmonium氯、{(R)- 3 -(2 -(1-cyclopropyl-methanoyloxy)-5-hydroxymethyl-pheny]-3-phenyl-propyl } -diisopropyl-ammonium氯、{(R)- 3 -(2 -(1-cyclobutyl-methanoyloxy)-5-hydroxymethyl-phenyl]-3-phenyl-propyl } -diisopropyl-ammonium氯、{(R)- 3 -(2 -(1-cyclopentyl-methanoyloxy)-5-hydroxymethyl-pheny]-3-phenyl-propyl } -diisopropyl-ammonium氯和{(R)- 3 -(2 -(1-cyclohexyl-methanoyloxy)-5-hydroxymethyl-phenyl]-3-phenyl-propyl } -diisopropyl-ammonium氯。 在這個(gè)化合物的本發(fā)明表達(dá)"烷基“最好是代表了一種straight-chain或branched-chain氫集團(tuán)在1到6 C-atoms。特殊偏好、乙酸乙酯、醋酸丙對(duì)甲基異丙酯、醋酸異丁,,,pentyl和hexyl。表達(dá)" cycloalkyl”指明周期性氫團(tuán)體,有3 - 10個(gè)氫原子,也可能包含了合適的替代品代替氫原子。 表達(dá)"苯基”指明了-C 6小時(shí)5 -group可替代或unsubstituted。合適的替代品,例如、醇酸、氧、鹵素,硝基和三聚氰胺。表達(dá)"中",就烷基的組成部分,已給以上含義相同的“烷基”。適合有氟、氯離子、鹵素溴碘原子 本發(fā)明也包括方法生產(chǎn)化合物的發(fā)明,按照一般公式我以及寶貴的中間體。 這個(gè)方法的特點(diǎn)是化學(xué)-和區(qū)域選擇性。 我的一般公式 在R代表C 1 -C 6 -alkyl、C 3 -C 10 -cycloalkyl取代苯、unsubstituted,或者是酸性渣X−的生理兼容的無機(jī)或有機(jī)酸,是那樣 • 一)的化合物啊。配方 用一個(gè)分裂形成一種化合物加氫劑的配方V嗎 于是 o b)的轉(zhuǎn)換公式,用了V的代理人,以給一組配方VI , o c)轉(zhuǎn)換為原料,經(jīng)�；瘎�,以為了得到的公式 在上述的意義[j]. d),與生理兼容無機(jī)物轉(zhuǎn)化為酸或有機(jī)化合物的形成 在R代表C 1 -C 6 -alkyl、C 3 -C 10 -cycloalkyl,unsubstituted或取代苯和X−是酸性渣的生理兼容的無機(jī)或有機(jī)酸。 依照這項(xiàng)發(fā)明,為制造的化合物的通用公式我鹽酸、hydrobromic酸、磷酸、硫酸、硝酸、醋酸、丙酸、酸、硬脂酸、馬來酸、富馬酸、草酸琥珀酸、DL-malic酸、L -(−-malic酸、D -(+)-malic酸、DL-tartaric酸、L -(+)-tartaric酸、D -(−-tartaric酸、檸檬酸、天冬氨酸、L -(+)-ascorbic酸、D -(+)-glucuronic酸、2-oxopropionic酸(丙酮酸),furan-2-carboxylic酸(mucic酸)、苯甲酸、4-hydroxybenzoic酸、salicyclic酸、vanillic酸、4-hydroxycinammic酸、沒食子酸、馬尿酸(N-benzoyl-glycine),aceturic酸(N-aectylglycine),phloretinic酸(3 -(4-hydroxyphenyl)-propionic酸)、鄰苯二甲酸、四種羧酸或orotic酸。 依照一個(gè)有利的進(jìn)一步發(fā)展的發(fā)明了一種化合物,R-configured制造的一般公式,二是描述, 在R代表C 1 -C 6 -alkyl、C 3 -C 10 -cycloalkyl取代苯、unsubstituted,或者是酸性渣X−的生理兼容的無機(jī)或有機(jī)酸,在那 • 一個(gè)復(fù)合的阿三級(jí)方程式 用一個(gè)分裂形成一種化合物加氫劑的配方 于是 o b)的轉(zhuǎn)換公式5所以取得與還原劑,為了給一個(gè)公式 , o c)轉(zhuǎn)換為原料,經(jīng)酰化劑,以為了獲得了一級(jí)方程式 在上述的意義[j],它 阿d)轉(zhuǎn)化為有生理兼容的無機(jī)或有機(jī)酸形成化合物的配方2 在R代表C 1 -C 6 -alkyl、C 3 -C 10 -cycloalkyl,unsubstituted或取代苯和X−是酸性渣的生理兼容的無機(jī)或有機(jī)酸。 為了獲得成分資料庫的通用公式,依照《中華人民共和國(guó)hydrobromic鹽酸、酸法、磷酸、硫酸、硝酸、醋酸、丙酸、酸、硬脂酸、馬來酸、富馬酸、草酸琥珀酸、DL-malic酸、L -(−-malic酸、D -(+)-malic酸、DL-tartaric酸、L -(+)-tartaric酸、D -(−-tartaric酸、檸檬酸、天冬氨酸、L -(+)-ascorbic酸、D -(+)-glucuronic酸、2-oxopropionic酸(丙酮酸),furan-2-carboxylic酸(mucic酸)、苯甲酸、4-hydroxybenzoic酸、salicyclic酸、vanillic酸、4-hydroxycinammic酸、沒食子酸、馬尿酸(N-benzoyl-glycine),aceturic酸(N-aectylglycine),phloretinic酸(3 -(4-hydroxyphenyl)-propionic酸)、鄰苯二甲酸、四種羧酸或orotic酸。 特定資料庫的基礎(chǔ)上,-4-benzyloxy-3水晶R -(− 是nzoic——(3-diisopropylamino-1-phenyl-propyl酸甲酯、高純度、中間產(chǎn)品的R -(3 -(3-diisopropylamino-phenyl-propyl−-4-hydroxy-benzo ic酸甲酯制備,降至R -(+)- 2 -(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethylp henol,終于在一個(gè)合適的方式、�；蜕砩先缓筠D(zhuǎn)換兼容無機(jī)或有機(jī)酸下結(jié)晶的自發(fā)的高純度、水晶、穩(wěn)定的鹽。根據(jù)酸氯化合物的一般公式,1, 在R代表C 1 -C 6 -alkyl,尤其是異丙醇、丙三-C 10 -cycloalkyl或unsubstituted或取代苯。 |
9樓2010-05-19 00:21:55
meng851124
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