96301-34-7

Basic information

• Product Name: atamestane
• Synonyms: 1-Methylandrosta-1,4-diene-3,17-dione;SH-489;(8R,9S,10S,13S,14S)-1,10,13-trimethyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3,17-dione
• CAS NO: 96301-34-7
• Molecular Formula: C₂₀H₂₆O₂
• Molecular Weight: 298.42
• Mol File: 96301-34-7.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 443°Cat760mmHg
• Flash Point: 165.2°C
• Appearance: /
• Density: 1.12g/cm³
• Vapor Pressure: 4.78E-08mmHg at 25°C
• Refractive Index: 1.561
• CAS DataBase Reference: atamestane(CAS DataBase Reference)
• NIST Chemistry Reference: atamestane(96301-34-7)
• EPA Substance Registry System: atamestane(96301-34-7)

Safety Data

• Hazardous Substances Data: 96301-34-7(Hazardous Substances Data)

Usage

Originator

Atamestane,Schering AG

Manufacturing Process

6.01 g of 17β-hydroxy-1-methylandrosta-1,4-dien-3-one is dissolved in 100 ml of acetone. At room temperature, 22 ml of a chromic acid solution (prepared from 6.67 g of CrO3, 6 ml of concentrated sulfuric acid, replenished with water to 100 ml) is added dropwise to this solution. The mixture is stirred for one hour and then precipitated into ice water, the product is suctioned off and dried, thus obtaining after recrystallization from acetone/hexane 5.25 g of 1-methylandrosta-1,4-diene-3,17-dione, melting point 165-166°C.

Therapeutic Function

Aromatase inhibitor

InChI:InChI=1/C20H26O2/c1-12-10-14(21)11-13-4-5-15-16-6-7-18(22)19(16,2)9-8-17(15)20(12,13)3/h10-11,15-17H,4-9H2,1-3H3/t15-,16-,17-,19-,20-/m0/s1

Upstream product

• 153-00-4 17β-hydroxy-1-methyl-5α-androst-1-en-3-one 
• 7750-80-3 17β-hydroxy-1-methyl-1,4-androstadiene-3-one 
• 1099-80-5 17β-acetoxy-1-methyl-androsta-1,4-dien-3-one 
• 4062-46-8 17β-acetyloxy-1α-methyl-5α-androstan-3-one 
• 169306-46-1 17β-acetoxy-2α,4α-dibromo-1α-methyl-5α-androstan-3-one 
• 128-37-0 2,6-di-tert-butyl-4-methyl-phenol 
• 897-06-3 Androsta-1,4-diene-3,17-dione 
• 75-24-1 trimethylaluminum 

Downstream Products

• 138548-87-5 C₂₉H₅₄O₂Si₄ 
• 138548-77-3 (3aS,4S,7aS)-4-[2-(5-Hydroxy-2,3-dimethyl-phenyl)-ethyl]-7a-methyl-octahydro-inden-1-one 

Relevant articles and documents

Synthesis of atamestane (SH 489): An aromatase inhibitor

Atamestane (SH 489) was synthesized from 17β-Acetyoxy-1α-methyl-5α-androstan-3-one. Thus dibromination followed by dehydrobromination of the A-ring have dienone (5) in good yield, which was hydrolyzed and oxidized to give the title compound in 60% overall yield.

2-iodo-3-keto-Δ4 steroids, process for their production, as well as their further processing

The new intermediate products of general formula I STR1 in which R1 stands for a hydrogen atom or a straight-chain or branched alkyl group with 1 to 4 carbon atoms, R2 stands for a hydrogen atom or a methyl group, R3 stands for a hydrogen atom, R4 stands for an acyloxy group with 1 to 4 carbon atoms in the acyl radical or R3 and R4 together stand for a keto-oxygen atom, are suitable in an excellent way for introducing a Δ1 double bond in the steroid skelton with the simultaneous presence of a Δ4 double bond, as well as a saturated carbonyl group, by clevage of hydrogen iodide with a base in an amidic solvent at elevated temperature. If R2 stands for a hydrogen atom, the A-ring is aromatized after the hydrogen iodide cleavage. For the production of a new intermediate products, special iodization processes, which partially also allow a stereoselective control of the iodization, are used.

Process for the preparation of 1-methylandrosta-1,4-diene-3,17,dione, and the novel intermediates for this process

1-Methylandrosta-1,4-diene-3,17-dione is prepared by a process wherein a 3-enol ester or 3-enol ether of general Formula II STR1 wherein R1 is an alkyl residue of 1-3 carbon atoms or an acyl or trialkylsilyl group of up to 10 carbon atoms in the group, is converted into the 2-bromo steroid of Formular III STR2 wherein the bromine substituent can be in the α- as well as in the β-position, and the compound of general Formula III is converted into 1-methylandrosta-1,4-diene-3,17-dione.