KR830007716A - Method for preparing 3-amide substituted steroid derivatives - Google Patents

Abstract

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Description

Method for preparing 3-amide substituted steroid derivatives

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Claims (7)

An amine such as the following formula (II) is reacted with a halide such as formula (III) to obtain a compound of formula (I) wherein R ₂ is hydrogen and R ₃ is an alkoxycarbonyl or acyl group having 2 to 8 carbon atoms. A product obtained by separating and chlorinating if necessary or reacting with a peptide or α-amino acid having 2 or 3 units of α-amino acid in which the amine group is protected by a group which can be readily cleaved by acid hydrolysis. To obtain a compound of formula (I), wherein R ₂ is hydrogen, R ₃ is a peptide having 2 or 3 units of α-amino acid or a group derived from α-amino acid, and is separated and chlorinated if necessary, or 2-5 carbon atoms, a hydroxyalkyl Harley and out C ₂ -C ₅ alkyl leads to a (wherein the halogen is chlorine, bromine, or iodine) by reaction with R ₂ is R ₃ is hydrogen, or an alkyl group having a carbon number of 1-5, Or carbon number Obtain a compound of formula (I) which is a hydroxy alkyl group of 2-5, separate and chlorine it, or when R ₃ is hydrogen, react with a halide such as the following formula (IV) to make R ₂ C _1- A compound of formula (I) wherein the alkyl group is C ₅ or a hydroxyalkyl group having 2 to ₅ carbon atoms and R ₃ is an alkyl group having 1 to 5 carbon atoms or a hydroxyalkyl having 2 to 5 carbon atoms or an acyloxy or acyl group having 2 to 8 carbon atoms. Or when R ₃ is hydrogen, the product obtained by reacting a preceding compound, such as formula (I), with a femide or α-amino acid containing 2 or 3 units of α-amino acid, and then R ₂ An alkyl group having 1 to 5 or a hydroxy alkyl group having 2 to 5 carbon atoms, R ₃ is a peptide derived from a peptide containing 2 or 3 units of α-amino acid or a compound derived from α-amino acid, and then obtained. To separate salt if necessary Method of producing a 3-amino-substituted steroid derivatives, such that the following formula (Ⅰ), characterized in that. In the above structural formula: W represents an ethylidene group together with hydrogen, a hydroxyl group, or X, X is an ethyl group, or I A group or, together with W, represents an ethylidene group and indicates that the corresponding group is present in either of α and B structures, R ₁ is hydrogen or methyl, R ₂ is hydrogen, an alkyl group having 1 to 5 carbon atoms, or a hydroxy alkyl group having 2 to 5 carbon atoms, R ₃ is derived from a peptide or α-amino containing hydrogen, an alkyl group of 1-5 carbon atoms, a hydroxyalkyl group of 2-5 carbon atoms, an alkoxycarbonyl group of 2-8 carbon atoms, or an α-amino acid of 2 or 3 units. As a group, at least one of R ₂ and R ₃ is not hydrogen, on the other hand, i) R ₁ is a methyl group, W and R ₂ are hydrogen, and X is If a group, R ₃ cannot represent a residue derived from methyl or an acyl group or aminocarboxylic acid, ii) R ₁ is methyl, W is hydrogen, R ₂ is methyl and X is In the case of a group, R <_3> cannot represent a methyl group or an acetyl group, iii) R ₁ is a methyl group, R ₂ and W are hydrogen, X is (The hydroxyl group at this time is a (s) structure) If the amino group is in the 3α position R ₃ can not represent a methyl, acetyl, or glycyl group, iv) W is hydrogen, X is When the group and the amino group are in the 3α round, the substituents R ₁ , R ₂ and R ₃ cannot simultaneously represent a methyl group, v) R ₂ and W are hydrogen, R ₁ is a methyl group, and X is (A hydroxyl group at this time is a (R) structure). When the amino group is in the 3α position, R ₃ cannot represent an ethoxycarbonyl, methyl, or acetyl group. vi) When R ₁ , R ₂ and R ₃ are methyl groups at the same time and the amino group is in the 3α position, W and X can form an ethylidene group. R ₃ ′ is an alkoxycarbonyl group or acyl group having 2 to 8 carbon atoms, R ₃ ″ is an alkyl group having 1 to 5 carbon atoms, a hydroxyalkyl group having 2 to 5 carbon atoms, or an alkoxycarbonyl group having 2 to 8 carbon atoms, and Hal Is chlorine, bromine or iodine. The method of claim 1, wherein the protecting group of the amino group is a tertiary butyloxycarbonyl group. X The method of claim 1, wherein a derivative of the compound of formula II which is a group is used as starting material. X The method of claim 1, wherein a derivative of the compound of formula III, which is a group, is used as starting material. The method of claim 1, wherein one of the derivatives of the compound of formula (I) is named. -(2S) 2-Amino N-[(20S) -hydroxy (5a) -pregnan-3 a-yl] 1H-indole 3-propanamide. -(2S) 2-Amino N-[(20S) -20-hydroxy (5α) -pregnan-3α) -yl] 1H-indole 3-propanamide. 2-amino N-[(20S) -20-hydroxy-19-nor (5α) -pregnan-3α-yl] acetamide, and 2-amino N-[(20S) -20-hydroxy ( 5α) -pregnan-3α-yl] N-methyl acetamide and addition salts thereof with inorganic or organic acids. A method for producing a composition characterized by containing at least one of a derivative of the compound of formula (I) or an addition salt thereof as an active ingredient. The method according to the above 6, wherein the active ingredient consists of (2S) 2-amino N-1 (20S) -20 hydroxy (5α) pregnin-3α-yl / 1H-indole3-protiamide. ※ Note: The disclosure is based on the initial application.