103335-41-7

Usage

Uses

Used in Pharmaceutical Industry:
METHYL 4-AZA-5ALPHA-ANDROSTA-1-EN-3-ONE-17BETA-CARBOXYLATE is used as an intermediate in the synthesis of Finasteride (F342000) and Dutasteride (D735000) for the treatment of benign prostatic hyperplasia, acne, seborrhea, female hirsutism, prostatitis, and prostatic carcinoma, and other hyperandrogenetic related disorders.
Used as Impurity:
METHYL 4-AZA-5ALPHA-ANDROSTA-1-EN-3-ONE-17BETA-CARBOXYLATE is also used as an impurity in Finasteride (F342000) and Dutasteride (D735000) to ensure the quality and purity of the final product.

InChI:InChI=1/C20H29NO3/c1-19-10-8-14-12(13(19)5-6-15(19)18(23)24-3)4-7-16-20(14,2)11-9-17(22)21-16/h9,11-16H,4-8,10H2,1-3H3,(H,21,22)/t12-,13-,14-,15+,16+,19-,20+/m0/s1

Upstream product

• 73671-92-8 3-oxo-4-aza-5α-androstane-17β-carboxylic acid methyl ester 
• 149198-45-8 methyl (2α,5α,17β)-2-iodo-3-oxo-4-aza-5-androstane-17-carboxylate 
• 67-56-1 methanol 
• 104239-97-6 3-Oxo-4-aza-5α-androst-1-ene-17β-carboxylic acid 
• 17697-12-0 benzeneseleninic anhydride 

Downstream Products

• 104239-97-6 3-Oxo-4-aza-5α-androst-1-ene-17β-carboxylic acid 
• 103335-44-0 Methyl 4-methyl-3-oxo-4-aza-5alpha-androst-1-ene-17beta-carboxamide 
• 1026013-15-9 (4aR,4bS,6aS,7S,9aS,9bS)-11a-Methoxy-4a,6a-dimethyl-2-oxo-2,4a,4b,5,6,6a,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-indeno[5,4-f]quinoline-7-carboxylic acid methyl ester 
• 73671-92-8 3-oxo-4-aza-5α-androstane-17β-carboxylic acid methyl ester 
• 827589-62-8 Methyl 4-p-methoxybenzyl-3-oxo-4-aza-5α-androst-1-ene-17β-carboxylate 
• 1796930-46-5 dutasteride 
• 606101-78-4 2-Fluoro-4-methyl-3-oxo-4-aza-5α-androst-1-ene-17β-carboxylic acid methyl ester 
• 606101-79-5 (5α,17β)-2-Fluoro-3-oxo-4-methyl-4-azaandrost-1-ene-17-carboxylic acid 
• 98319-26-7 finasteride 
• 496947-19-4 3-Oxo-4-phenyl-4-aza-5α-androst-1-ene-17β-carboxylic acid 
• 166896-63-5 Methyl 3-oxo-4-azaandrosta-1,5,7-triene-17β-carboxylate 
• 166896-62-4 Methyl 3-oxo-4-azaandrosta-1,5-diene-17β-carboxylate 
• 138689-15-3 (5α,17β)-N-Methoxy-N-methyl-3-oxo-4-aza-androst-1-ene-17β-carboxamide 

Relevant academic research and scientific papers

A method of preparation he male amine

The invention belongs to the field of pharmaceutical chemistry, and relates to a high-yield method for preparing dutasteride, which comprises the following steps: (1) under the action of a catalyst, reacting aza-5-androst-1-alkenyl-3-keto-17beta-carboxylic acid (I) with alcohol to generate 4-aza-5-androst-1-alkenyl-3-keto-17beta-carboxylate (II); and (2) in the presence of a catalyst, reacting the 4-aza-5-androst-1-alkenyl-3-keto-17beta-carboxylate (II) with 2,5-ditrifluoromethylaniline in an organic solvent at certain reaction temperature to obtain the dutasteride (III) at high yield. The method has the characteristics of accessible raw material, mild reaction conditions and high product yield, and is easy to control.

Method for forming double bonds between 1-position and 2-position during synthesis of finasteride and dutasteride

The invention provides a method for forming double bonds between the 1-position and the 2-position during synthesis of finasteride and dutasteride. According to the process, a dihydrogen finasteride iodide and a dihydrogen dutasteride iodide are oxidized by oxone for systhesis of finasteride and dutasteride, and the method has the characteristics that reaction operation is simple and convenient, raw materials are low in price and easy to obtain, and the yield and the purity are high. In particular, oxone is non-toxic, stable, easy to operate and more suitable for large-scale industrial production, and reagents which are harmful to the environment and high in price are avoided. The method can be further applied to forming of double bonds between the 1-position and the 2-position of an intermediate in other finasteride and dutasteride processes. The invention further provides a synthesis method of dihydrogen dutasteride; according to the method, a corresponding ester raw material has a one-pot reaction with 2,5-bis(trifluoromethyl)aniline under the activation of boron tribromide, and dihydrogen dutasteride with the yield of 93% is obtained.

PROCESS FOR PREPARING ANDROSTENONE DERIVATIVES

Provided is a process for preparing androstenone derivatives, specifically 3-oxo-4-aza-5α-androstene-17β-carboxylic acid of Formula I, a key intermediate for dutasteride.

METHOD OF PRODUCING 17BETA-(SUBSTITUTED)-3-OXO-DELTA 1,2-4-AZASTEROIDS AND INTERMEDIATES

The 17β-(substituted)-3-oxo-Δ1,2-azasteroids (I), wherein R1 is C1-C4 alkyl, OR2, wherein R2 is a C1-C4 alkyl radical, or NR3R4 , wherein R3 and R4, equal or different, represent hydrogen or a C1-C4 alkyl radical, can be obtained by means of a process comprising cleaving the oxazolidinedione ring present in a 2-(substituted)-3-hydroxyoxazolidinedione of formula (IV), wherein R5 is Br or trichloromethylsulfonyl, and removing the substituent at position 2, to form a double bond at position 1,2. Some compounds (I) are testosterone-5α-reductase inhibitors and can be used in the treatment of hyperandrogenic disorders.

Method of prevention of prostatic carcinoma with 17β-N-monosubstituted-carbamoyl-4-aza-5α-androst-1-en-3-ones

17β-N-monosubstituted-carbamoyl-4-aza-5α-androst-1-en-3-ones of the formula wherein R1is selected from hydrogen, methyl and ethyl and R2is a straight or branched chain alkyl, cycloalkyl, aralkyl of from 1-12 carbons, or monocyclic aryl optionally containing 1 or more lower alkyl substituents of 1-2 carbon atoms and/or 1 or more halogens, and R′, R″, R″′ are hydrogen or methyl are useful for the prevention of prostatic carcinoma.

Method of treatment for prostatic cancer

Disclosed is a new treatment for men with prostatic cancer involving combination therapy of a 5α-reductase inhibitor, i.e., a 17β-substituted 4-azasteroid, a 17β-substituted non-azasteroid, 17β-acyl-3-carboxyandrost-3,5-diene, benzoylaminophenoxybutanoic acid derivative, fused benz(thio)amide or cinnamoylamide derivative, aromatic 1,2-diethers or thioethers, aromatic ortho acylaminophenoxy alkanoic acids, ortho thioalkylacylamino-phenoxy alkanoic acids, pharmaceutically acceptable salts and esters thereof, and particularly finasteride, in combination with an antiandrogen, i.e. flutamide. Pharmaceutical compositions useful for treatment are also disclosed.

Method of treatment for benign prostatic hyperplasia

Disclosed is an improved treatment for men with benign prostatic hyperplasia (BPH), involving combination therapy of a 5α-reductase inhibitor, e.g. a 17β-substituted 4-azasteroid, a 17β-substituted non-azasteroid, 17β-acyl-3-carboxy-androst-3,5-diene, benzoylaminophenoxybutanoic acid derivative, fused benz(thio)amide or cinnamoylamide derivative, aromatic 1,2-diethers or thioethers, aromatic ortho acylaminophenoxy alkanoic acids, ortho thioalkylacylaminophenoxy alkanoic acids, pharmaceutically acceptable salts and esters thereof, and particularly finasteride, in combination with an α1 -adrenergic receptor blocker, i.e., terazosin. The combination provides therapy at the molecular level for the underlying cause of the disease as well as providing symptomatic relief. Pharmaceutical compositions useful for treatment are also disclosed.

Method of treatment of chronic prostatitis with 17β-N-monosubstituted-carbamoyl-4-aza-5α-androst-1-en-3-ones

The present invention is concerned with the use of 17β-N-monosubstituted-carbamaoyl-4-aza-5α-androst-1-en-3-one compounds as testosterone-5α-reductase inhibitors for the treatment of chronic prostatitis.

Substituted 4-aza-5α-androstan-ones as 5α-reductase inhibitors

Described are new 16-substituted and 7,16-disubstituted 4-aza-5α-androstan-3-ones and related compounds as 5α-reductase inhibitors.

17B-N-Substituted adamantyl/norbonanyl carbamoyl-4-aza-5a-and-rost-1-en-3-ones and androstan-3 ones

17 beta-N-substituted adamantyl/norbornanyl carbamoyl-4-aza-5alpha-androst-1-en-3-ones and androstan-3-ones as 5alpha-reductase inhibitors of the formula I