3764-87-2

Basic information

• Product Name: Trestolone
• Synonyms: 19-nor-7a-methyltestosterone;7-ALPHA-METHYL-19-NORTESTOSTERONE;(7r)-17-hydroxy-7,13-dimethyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-one;4-ESTREN-7-ALPHA-METHYL-17-BETA-OL-3-ONE;TRESTOLONE;17β-Hydroxy-7α-methylestr-4-en-3-one;7α-Methyl-19-nortestosterone;7α-Methyl-19-NT
• CAS NO: 3764-87-2
• Molecular Formula: C₁₉H₂₈O₂
• Molecular Weight: 288.42
• Product Categories: Steroid and Hormone
• Mol File: 3764-87-2.mol

Chemical Properties

• Melting Point: 145-146 °C
• Boiling Point: 375.48°C (rough estimate)
• Flash Point: 187.3°C
• Appearance: /
• Density: 0.9447 (rough estimate)
• Vapor Pressure: 1.44E-09mmHg at 25°C
• Refractive Index: 1.6220 (estimate)
• PKA: 15.06±0.60(Predicted)
• Water Solubility: 92mg/L(37 oC)
• CAS DataBase Reference: Trestolone(CAS DataBase Reference)
• NIST Chemistry Reference: Trestolone(3764-87-2)
• EPA Substance Registry System: Trestolone(3764-87-2)

Safety Data

• Hazardous Substances Data: 3764-87-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Trestolone is used as a potential hormonal male contraceptive method for inducing a state of temporary infertility. By mimicking the effects of testosterone, it can help regulate hormone levels and prevent sperm production, thus providing a non-invasive and reversible option for male contraception.

InChI:InChI=1/C19H28O2/c1-11-9-12-10-13(20)3-4-14(12)15-7-8-19(2)16(18(11)15)5-6-17(19)21/h10-11,14-18,21H,3-9H2,1-2H3

Synthetic route

17β-[(tert-butyldimethylsilyl)oxy]-7α-methylestr-4-en-3-one → 7α-methyl-19-nortestosterone (3764-87-2)

Conditions	Yield
With water; sulfuric acid In acetone at 20℃; for 48h;	85%

C21H30O3 → 7beta-Methyl-19-nortestosterone + 7α-methyl-19-nortestosterone (3764-87-2)

Conditions	Yield
With water; potassium hydroxide In methanol; toluene at 40℃; for 2h; Inert atmosphere;	A 3% B 60.5%

7alpha-Methyl-19-nortestosterone acetate (6157-87-5) → 7α-methyl-19-nortestosterone (3764-87-2)

Conditions	Yield
Stage #1: 7alpha-Methyl-19-nortestosterone acetate With methanol; potassium hydroxide for 3 - 4h; Stage #2: With citric acid pH=6;

19-nortestosterone (434-22-0) → 7beta-Methyl-19-nortestosterone + 7α-methyl-19-nortestosterone (3764-87-2)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: perchloric acid / ethyl acetate; water / 8 h / 18 °C / Inert atmosphere 2.1: N-Bromosuccinimide / water; N,N-dimethyl-formamide / 1.17 h / 0 - 7 °C / Inert atmosphere 2.2: 1.58 h / 110 °C / Inert atmosphere 3.1: copper(l) iodide / tetrahydrofuran; Dimethyl ether / 0.5 h / 0 - 10 °C / Inert atmosphere 4.1: potassium hydroxide; water / methanol; toluene / 2 h / 40 °C / Inert atmosphere View Scheme

3,17β-diacetoxy-estra-3,5-diene (4999-76-2) → 7beta-Methyl-19-nortestosterone + 7α-methyl-19-nortestosterone (3764-87-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: N-Bromosuccinimide / water; N,N-dimethyl-formamide / 1.17 h / 0 - 7 °C / Inert atmosphere 1.2: 1.58 h / 110 °C / Inert atmosphere 2.1: copper(l) iodide / tetrahydrofuran; Dimethyl ether / 0.5 h / 0 - 10 °C / Inert atmosphere 3.1: potassium hydroxide; water / methanol; toluene / 2 h / 40 °C / Inert atmosphere View Scheme

7α-methyl-19-nortestosterone (3764-87-2) + ethylene glycol (107-21-1) → 7α-methyl-3,3-(ethylenedioxy)-5(10)-estren-7-ol (141664-11-1)

Conditions	Yield
With toluene-4-sulfonic acid; orthoformic acid triethyl ester In benzene at 72℃; for 1.5h;

7α-methyl-19-nortestosterone (3764-87-2) + ethylene glycol (107-21-1) → 7α-methyl-3,3-(ethylenedioxy)-5(10)-estren-7-ol (141664-11-1) + C21H32O3

Conditions	Yield
With toluene-4-sulfonic acid In benzene for 43h; Heating; Title compound not separated from byproducts;

7α-methyl-19-nortestosterone (3764-87-2) + ethylene glycol (107-21-1) → 7α-methyl-3,3-(ethylenedioxy)-5(10)-estren-17-one (141664-12-2) + 3,3-ethylenedioxy-7α-methyl-5-estren-17-one

Conditions	Yield
With sodium acetate; toluene-4-sulfonic acid; pyridinium chlorochromate 1.) benzene, reflux, 43 h, 2.) CH2Cl2, RT, 5.5 h; Yield given. Multistep reaction;
With sodium acetate; toluene-4-sulfonic acid; pyridinium chlorochromate 1.) benzene, reflux, 43 h, 2.) CH2Cl2, RT, 5.5 h; Yield given. Multistep reaction. Title compound not separated from byproducts;

7α-methyl-19-nortestosterone (3764-87-2) + ethylene glycol (107-21-1) + lithium acetylide (70277-75-7) → 7α-methyl-17α-ethinyl-17β-hydroxy-4-estren-3-one (1162-60-3)

Conditions	Yield
Multistep reaction;

7α-methyl-19-nortestosterone (3764-87-2) + ethylene glycol (107-21-1) + lithium acetylide (70277-75-7) → 7α-methylnorethynodrel ethylene ketal (677299-58-0) + C23H32O3

Conditions	Yield
With sodium acetate; toluene-4-sulfonic acid; ethylenediamine; pyridinium chlorochromate Multistep reaction. Title compound not separated from byproducts;

7α-methyl-19-nortestosterone (3764-87-2) + methyllithium (917-54-4) → (7S,8R,9S,10R,13S,14S,17S)-3,7,13-Trimethyl-2,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-ol

Conditions	Yield
(i) THF, Et2O, (ii) aq. HCl, acetone; Multistep reaction;

7α-methyl-19-nortestosterone (3764-87-2) → (7S,8R,9S,10R,13S,14S,17S)-7,13-Dimethyl-2,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-ol

Conditions	Yield
(i) LiAlH4, THF, (ii) aq. HCl, acetone; Multistep reaction;

7α-methyl-19-nortestosterone (3764-87-2) + phenyllithium (591-51-5) → (7S,8R,9S,10R,13S,14S,17S)-7,13-Dimethyl-3-phenyl-2,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-ol

Conditions	Yield
(i) THF, Et2O, (ii) aq. HCl, acetone; Multistep reaction;

3,3-Dimethylacryloyl chloride (3350-78-5) + 7α-methyl-19-nortestosterone (3764-87-2) → 3-Methyl-but-2-enoic acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

(Z)-9-octadecenoyl chloride (112-77-6) + 7α-methyl-19-nortestosterone (3764-87-2) → (Z)-Octadec-9-enoic acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

Cyclopentanecarboxylic acid chloride (4524-93-0) + 7α-methyl-19-nortestosterone (3764-87-2) → Cyclopentanecarboxylic acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

n-dodecanoyl chloride (112-16-3) + 7α-methyl-19-nortestosterone (3764-87-2) → Dodecanoic acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

Nonanoyl chloride (764-85-2) + 7α-methyl-19-nortestosterone (3764-87-2) → Nonanoic acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

undec-10-enoyl chloride (38460-95-6) + 7α-methyl-19-nortestosterone (3764-87-2) → Undec-10-enoic acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

(E)-dec-2-enoyl chloride (110232-46-7) + 7α-methyl-19-nortestosterone (3764-87-2) → (E)-Dec-2-enoic acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

trans-chrotonyl chloride (625-35-4, 3488-22-0, 10487-71-5) + 7α-methyl-19-nortestosterone (3764-87-2) → (E)-But-2-enoic acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

3,3-dimethylbutanoic acid chloride (7065-46-5) + 7α-methyl-19-nortestosterone (3764-87-2) → 3,3-Dimethyl-butyric acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

pent-4-enoyl chloride (39716-58-0) + 7α-methyl-19-nortestosterone (3764-87-2) → Pent-4-enoic acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

chlorure d'acide ethyl-2 butyrique (2736-40-5) + 7α-methyl-19-nortestosterone (3764-87-2) → 2-Ethyl-butyric acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

undecanoyl chloride (17746-05-3) + 7α-methyl-19-nortestosterone (3764-87-2) → (7α,17β)-7-methyl-17-[(1-oxoundecyl)oxy]estr-4-en-3-one

Conditions	Yield
With pyridine at 20℃;
With sulfuric acid In ethyl acetate

heptadecanoyl chloride (40480-10-2) + 7α-methyl-19-nortestosterone (3764-87-2) → Heptadecanoic acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

cyclopentanepropanoyl chloride (104-97-2) + 7α-methyl-19-nortestosterone (3764-87-2) → 3-Cyclopentyl-propionic acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

Benzyloxyacetyl chloride (19810-31-2) + 7α-methyl-19-nortestosterone (3764-87-2) → Benzyloxy-acetic acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

4-heptylbenzoyl chloride (50606-96-7) + 7α-methyl-19-nortestosterone (3764-87-2) → 4-Heptyl-benzoic acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

p-ethylbenzoyl chloride (16331-45-6) + 7α-methyl-19-nortestosterone (3764-87-2) → 4-Ethyl-benzoic acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

4-propylbenzoyl chloride (52710-27-7) + 7α-methyl-19-nortestosterone (3764-87-2) → 4-Propyl-benzoic acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

4-butylbenzoyl chloride (28788-62-7) + 7α-methyl-19-nortestosterone (3764-87-2) → 4-Butyl-benzoic acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

4-pentylbenzoyl chloride (49763-65-7) + 7α-methyl-19-nortestosterone (3764-87-2) → 4-Pentyl-benzoic acid (7R,8R,9S,10R,13S,14S,17S)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With pyridine at 20℃;

Upstream product

• 6157-87-5 7alpha-Methyl-19-nortestosterone acetate 
• 434-22-0 19-nortestosterone 
• 4999-76-2 3,17β-diacetoxyoestra-3,5-diene 

Downstream Products

• 141664-12-2 3,3-ethylenedioxy-7α-methyl-5(10)-estren-17-one 
• 1162-60-3 7α-methyl-17α-ethinyl-17β-hydroxy-4-estren-3-one 
• 677299-58-0 7α-methylnorethynodrel ethylene ketal 

Relevant articles and documents

Process for the production of 7alpha-methyl steroids

This invention relates to a process for the production of 7α-methyl steroids of general formula I, starting from compounds of general formula II, which are reacted in an aprotic solvent in the presence of 1-30 mol % of a copper compound CuYnLm with 1-3 molar equivalents of CH3MgX, then with a strong acid. The process according to the invention is distinguished in that 7α-methyl steroids are obtained in good yields as well as high chemical purity and high diastereomer purities. The process is distinguished in that less waste accumulates with considerably higher throughput. The process according to the invention can therefore be suitable for the production of 7α-methyl steroids on the industrial scale.

Optimization of copper(I)-catalyzed 1,6-conjugate addition of a methyl group to 17β-acetoxy-4,6-estradien-3-one

7α-Methyl-19-nortestosterone (1) was synthesized from 19-nortestosterone (2) via 17β-acetoxy-4,6-estradien-3-one (4). The critical parameters for the synthesis of compound (1) have been identified. An optimization procedure consisting of an iterative, two-stage reaction response surface analysis was carried out. As a result, the synthesis of the target compound (1) from the intermediate (4) was achieved under the newly determined conditions, in a repeatable manner. This afforded compound (1) in an yield of over 60%, essentially free from the 7β-Me isomer (6), under experimental conditions amenable for scale enhancement.

Method for androgen supplementation

A particular group of androgens is not metabolized to their 5α-reduced form in the prostate and other tissues. Thus, administration of these compounds--testosterone derivatives with a non-hydrogen substituent in the 6α or 7α position--allows one to provide androgen supplementation therapy without stimulating abnormal prostate growth. A preferred compound for use in the invention is 7α-methyl-19-nortestosterone.

Method for the control of fertility

7α-Methylestr-4-ene-3α,17β-diol and derivatives thereof useful as antifertility agents.