2137-18-0

Basic information

• Product Name: Gestonorone
• Synonyms: GESTONORONE;19-NOR-4-PREGNEN-17-OL-3,20-DIONE;17-hydroxy-19-norpregn-4-ene-3,20-dione;17ALPHA-HYDROXY-19-NORPREGN-4-EN-3,20-DIONE;17a-hydroxy-19-norprogesterone;17-alpha-hydroxy-19-norpregn-4-ene-3,20-dione;GESTONORONE BASE:17ALPHA-HYDROXY-19-NORPREGN-4-EN-3,20-DIONE;19-Nor-4-pregene-17-ol-3,20-dione
• CAS NO: 2137-18-0
• Molecular Formula: C₂₀H₂₈O₃
• Molecular Weight: 316.43
• EINECS: 218-378-2
• Product Categories: Steroids
• Mol File: 2137-18-0.mol
• Article Data: 4

Chemical Properties

• Melting Point: 222-224°C
• Boiling Point: 484.9 °C at 760 mmHg
• Flash Point: 261.2 °C
• Appearance: White or almost white crystalline powder
• Density: 1.17
• Vapor Pressure: 1.95E-11mmHg at 25°C
• Refractive Index: 1.564
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 13.03±0.40(Predicted)
• CAS DataBase Reference: Gestonorone(CAS DataBase Reference)
• NIST Chemistry Reference: Gestonorone(2137-18-0)
• EPA Substance Registry System: Gestonorone(2137-18-0)

Safety Data

• Hazardous Substances Data: 2137-18-0(Hazardous Substances Data)

Usage

Uses

Gestonorone is a steroidal progestin. It has been shown to have accelerated body weight gain and caused the atrophy of the prostate, uterus, and seminal vesicles in rats. It is also an inhibitor of the reductive pathway of Testosterone (T155000) metabolism.

InChI:InChI=1/C20H28O3/c1-12(21)20(23)10-8-18-17-5-3-13-11-14(22)4-6-15(13)16(17)7-9-19(18,20)2/h11,15-18,23H,3-10H2,1-2H3

Synthetic route

C20H27ClO3 → 17-alpha-Hydroxy-19-norprogesterone (2137-18-0)

Conditions	Yield
With iron; acetic acid at 60℃; for 3h; Reagent/catalyst; Temperature;	97.97%

20,20-ethanediyldioxy-3-methoxy-19-nor-pregna-2,5(10)-dien-17-ol (14339-99-2) → 17-alpha-Hydroxy-19-norprogesterone (2137-18-0)

Conditions	Yield
With hydrogenchloride

17α-hydroxy-3-methoxy-19-norpregna-1,3,5(10)-trien-20-one (1624-58-4) → 17-alpha-Hydroxy-19-norprogesterone (2137-18-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: benzene; toluene-4-sulfonic acid / Entfernen des entstehenden Wassers 2: diethyl ether; lithium; liquid ammonia / anschliessend Behandeln mit Aethanol 3: methanol.HCl View Scheme
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid; trimethyl orthoformate / dichloromethane / 2 h / 20 °C 2: sodium; ammonia / ethanol; water; tetrahydrofuran; tert-butyl alcohol / -60 °C / Inert atmosphere 3: hydrogenchloride / water; tetrahydrofuran / 0.33 h / 60 °C View Scheme

3-hydroxy-19-norpregna-1,3,5(10),16-tetraen-20-one (101766-63-6) → 17-alpha-Hydroxy-19-norprogesterone (2137-18-0)

Conditions	Yield
Multi-step reaction with 6 steps 1: methanol; aqueous hydrogen peroxide; aq. NaOH solution 2: ethanol; aqueous KOH-solution 3: HBr; acetic acid / Hydrierung an Palladium/CaCO3 in Aethanol 4: benzene; toluene-4-sulfonic acid / Entfernen des entstehenden Wassers 5: diethyl ether; lithium; liquid ammonia / anschliessend Behandeln mit Aethanol 6: methanol.HCl View Scheme

16α,17α-epoxy-17-acetyl-Δ1,3,5(10)-estratriene (67519-64-6) → 17-alpha-Hydroxy-19-norprogesterone (2137-18-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: ethanol; aqueous KOH-solution 2: HBr; acetic acid / Hydrierung an Palladium/CaCO3 in Aethanol 3: benzene; toluene-4-sulfonic acid / Entfernen des entstehenden Wassers 4: diethyl ether; lithium; liquid ammonia / anschliessend Behandeln mit Aethanol 5: methanol.HCl View Scheme

16α,17-epoxy-3-methoxy-19-nor-pregna-1,3,5(10)-trien-20-one (111979-17-0) → 17-alpha-Hydroxy-19-norprogesterone (2137-18-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: HBr; acetic acid / Hydrierung an Palladium/CaCO3 in Aethanol 2: benzene; toluene-4-sulfonic acid / Entfernen des entstehenden Wassers 3: diethyl ether; lithium; liquid ammonia / anschliessend Behandeln mit Aethanol 4: methanol.HCl View Scheme

20,20-(ethylenedioxy)-3-methoxy-17α-hydroxy-19-norpregna-1,3,5(10)-triene (14328-46-2) → 17-alpha-Hydroxy-19-norprogesterone (2137-18-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: diethyl ether; lithium; liquid ammonia / anschliessend Behandeln mit Aethanol 2: methanol.HCl View Scheme
Multi-step reaction with 2 steps 1: sodium; ammonia / ethanol; water; tetrahydrofuran; tert-butyl alcohol / -60 °C / Inert atmosphere 2: hydrogenchloride / water; tetrahydrofuran / 0.33 h / 60 °C View Scheme

Estrone (53-16-7) → 17-alpha-Hydroxy-19-norprogesterone (2137-18-0)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: sodium hydroxide / acetone; water / 2 h / Reflux 2.1: potassium tert-butylate / tetrahydrofuran / 0 - 20 °C 3.1: triethylamine / dichloromethane / 2 h / 0 - 20 °C 4.1: sodium methylate / methanol / Reflux 4.2: 2 h / Reflux 5.1: toluene-4-sulfonic acid; trimethyl orthoformate / dichloromethane / 2 h / 20 °C 6.1: sodium; ammonia / ethanol; water; tetrahydrofuran; tert-butyl alcohol / -60 °C / Inert atmosphere 7.1: hydrogenchloride / water; tetrahydrofuran / 0.33 h / 60 °C View Scheme

estrone 3-methyl ether (1624-62-0) → 17-alpha-Hydroxy-19-norprogesterone (2137-18-0)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: potassium tert-butylate / tetrahydrofuran / 0 - 20 °C 2.1: triethylamine / dichloromethane / 2 h / 0 - 20 °C 3.1: sodium methylate / methanol / Reflux 3.2: 2 h / Reflux 4.1: toluene-4-sulfonic acid; trimethyl orthoformate / dichloromethane / 2 h / 20 °C 5.1: sodium; ammonia / ethanol; water; tetrahydrofuran; tert-butyl alcohol / -60 °C / Inert atmosphere 6.1: hydrogenchloride / water; tetrahydrofuran / 0.33 h / 60 °C View Scheme

C22H32O4 → 17-alpha-Hydroxy-19-norprogesterone (2137-18-0)

Conditions	Yield
With hydrogenchloride In tetrahydrofuran; water at 60℃; for 0.333333h;	18.6 g

mestranol (72-33-3) → 17-alpha-Hydroxy-19-norprogesterone (2137-18-0)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: triethylamine / dichloromethane / 2 h / 0 - 20 °C 2.1: sodium methylate / methanol / Reflux 2.2: 2 h / Reflux 3.1: toluene-4-sulfonic acid; trimethyl orthoformate / dichloromethane / 2 h / 20 °C 4.1: sodium; ammonia / ethanol; water; tetrahydrofuran; tert-butyl alcohol / -60 °C / Inert atmosphere 5.1: hydrogenchloride / water; tetrahydrofuran / 0.33 h / 60 °C View Scheme

3-methoxy-21-(phenylsulfinyl)-19-norpregna-1(2),3(4),5(10),17(20),20-pentaene → 17-alpha-Hydroxy-19-norprogesterone (2137-18-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium methylate / methanol / Reflux 1.2: 2 h / Reflux 2.1: toluene-4-sulfonic acid; trimethyl orthoformate / dichloromethane / 2 h / 20 °C 3.1: sodium; ammonia / ethanol; water; tetrahydrofuran; tert-butyl alcohol / -60 °C / Inert atmosphere 4.1: hydrogenchloride / water; tetrahydrofuran / 0.33 h / 60 °C View Scheme

3-methoxy-17α-[(trimethylsilyl)oxy]estr-2,5(10)-dien-17-carbonitrile + methyllithium (917-54-4) → 17-alpha-Hydroxy-19-norprogesterone (2137-18-0)

Conditions	Yield
Stage #1: 3-methoxy-17α-[(trimethylsilyl)oxy]estr-2,5(10)-dien-17-carbonitrile; methyllithium With N,N,N,N,-tetramethylethylenediamine In tert-butyl methyl ether at -40 - -30℃; for 1h; Stage #2: With hydrogenchloride In tert-butyl methyl ether at -30 - 25℃; for 16h;	25.67 g

3-methoxyestra-2,5(10)-dien-17-one (17976-32-8) → 17-alpha-Hydroxy-19-norprogesterone (2137-18-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 2,6-di-tert-butyl-4-methyl-phenol / ethanol / 0.17 h / Inert atmosphere 1.2: 17 h / 20 - 63 °C / Inert atmosphere 2.1: 2,6-di-tert-butyl-4-methyl-phenol; 1H-imidazole / tert-butyl methyl ether; tetrahydrofuran / Inert atmosphere 3.1: N,N,N,N,-tetramethylethylenediamine / tert-butyl methyl ether / 1 h / -40 - -30 °C 3.2: 16 h / -30 - 25 °C View Scheme

C22H33ClO3Si → 17-alpha-Hydroxy-19-norprogesterone (2137-18-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium diisobutylamide; chloro-trimethyl-silane; n-butyllithium / dichloromethane; chloroform / 1 h / -50 °C / Inert atmosphere 2: iron; acetic acid / 3 h / 60 °C View Scheme

estra-4-ene-3,17-dione (734-32-7) → 17-alpha-Hydroxy-19-norprogesterone (2137-18-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium hydroxide; Tetrahydrothiopyran-4-one; acetic acid / methanol; ethanol / 25 h / 38 °C / Green chemistry 2: dmap / dichloromethane / 2 h / 32 °C 3: lithium diisobutylamide; chloro-trimethyl-silane; n-butyllithium / dichloromethane; chloroform / 1 h / -50 °C / Inert atmosphere 4: iron; acetic acid / 3 h / 60 °C View Scheme
Multi-step reaction with 4 steps 1: sodium hydroxide; Tetrahydrothiopyran-4-one; acetic acid / methanol; ethanol / 25 h / 38 °C / Green chemistry 2: triethylamine / tetrachloromethane / 2 h / -6 °C 3: lithium diisobutylamide; chloro-trimethyl-silane; n-butyllithium / dichloromethane; chloroform / 1 h / -50 °C / Inert atmosphere 4: iron; acetic acid / 3 h / 60 °C View Scheme
Multi-step reaction with 4 steps 1: sodium hydroxide; Tetrahydrothiopyran-4-one; acetic acid / methanol; ethanol / 25 h / 38 °C / Green chemistry 2: 1,8-diazabicyclo[5.4.0]undec-7-ene / benzene / 2 h / 0 - 2 °C 3: lithium diisobutylamide; chloro-trimethyl-silane; n-butyllithium / dichloromethane; chloroform / 1 h / -50 °C / Inert atmosphere 4: iron; acetic acid / 3 h / 60 °C View Scheme

17β-cyano-17α-hydroxy-19-norandrost-4-en-3-one → 17-alpha-Hydroxy-19-norprogesterone (2137-18-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: dmap / dichloromethane / 2 h / 32 °C 2: lithium diisobutylamide; chloro-trimethyl-silane; n-butyllithium / dichloromethane; chloroform / 1 h / -50 °C / Inert atmosphere 3: iron; acetic acid / 3 h / 60 °C View Scheme
Multi-step reaction with 3 steps 1: triethylamine / tetrachloromethane / 2 h / -6 °C 2: lithium diisobutylamide; chloro-trimethyl-silane; n-butyllithium / dichloromethane; chloroform / 1 h / -50 °C / Inert atmosphere 3: iron; acetic acid / 3 h / 60 °C View Scheme
Multi-step reaction with 3 steps 1: 1,8-diazabicyclo[5.4.0]undec-7-ene / benzene / 2 h / 0 - 2 °C 2: lithium diisobutylamide; chloro-trimethyl-silane; n-butyllithium / dichloromethane; chloroform / 1 h / -50 °C / Inert atmosphere 3: iron; acetic acid / 3 h / 60 °C View Scheme
Multi-step reaction with 3 steps 1: dmap; 1H-imidazole / toluene; acetone / 2 h / -1 - 0 °C 2: lithium diisobutylamide; chloro-trimethyl-silane; n-butyllithium / dichloromethane; chloroform / 1 h / -50 °C / Inert atmosphere 3: iron; acetic acid / 3 h / 60 °C View Scheme

17-alpha-Hydroxy-19-norprogesterone (2137-18-0) + acetic anhydride (108-24-7) → 17α-acetoxy-19-norpregna-4-ene-3,20-dione (31981-44-9)

Conditions	Yield
With toluene-4-sulfonic acid at 20℃; for 24h;	95%
With toluene-4-sulfonic acid und Behandeln des Reaktionsprodukts mit methanol.KOH;
With toluene-4-sulfonic acid und Behandeln des Reaktionsprodukts mit methanol.HCl;

Isopropenyl acetate (108-22-5) + 17-alpha-Hydroxy-19-norprogesterone (2137-18-0) → 17α-acetoxy-19-norpregna-4-ene-3,20-dione (31981-44-9)

Conditions	Yield
Stage #1: Isopropenyl acetate; 17-alpha-Hydroxy-19-norprogesterone With toluene-4-sulfonic acid In dichloromethane; chloroform at 58 - 60℃; for 2h; Stage #2: With hydrogenchloride In dichloromethane; chloroform; water at 60℃; Solvent; Temperature;	82.36%

17-alpha-Hydroxy-19-norprogesterone (2137-18-0) + orthoformic acid triethyl ester (122-51-0) → 3-ethoxy-17α-hydroxy-19-norpregna-4-en-20-one

Conditions	Yield
With toluene-4-sulfonic acid In ethanol at 20 - 80℃; for 1h;	82%

n-hexanoic anhydride (2051-49-2) + 17-alpha-Hydroxy-19-norprogesterone (2137-18-0) → gestonorone caproate (1253-28-7)

Conditions	Yield
With toluene-4-sulfonic acid und anscliessendes Erwaermen mit methanol.HCl;

17-alpha-Hydroxy-19-norprogesterone (2137-18-0) → 11β,17,21-trihydroxy-19-nor-pregn-4-ene-3,20-dione (54947-44-3)

Conditions	Yield
mit Hilfe von Homogenaten aus Nebennieren;
Multi-step reaction with 3 steps 1: THF; methanol; iodine / anschliessendes Behandeln mit wss.NaOH und Erwaermen des Reaktionsprodukts mit Kaliumacetat in Aceton 2: aqueous methanol.KHCO3 3: mit Hilfe von Homogenaten aus Nebennieren View Scheme

17-alpha-Hydroxy-19-norprogesterone (2137-18-0) → 21-acetoxy-17-hydroxy-19-nor-pregn-4-ene-3,20-dione (124263-28-1)

Conditions	Yield
With tetrahydrofuran; methanol; iodine anschliessendes Behandeln mit wss.NaOH und Erwaermen des Reaktionsprodukts mit Kaliumacetat in Aceton;

formic acid (64-18-6) + 17-alpha-Hydroxy-19-norprogesterone (2137-18-0) + acetic anhydride (108-24-7) → 17-formyloxy-19-nor-pregn-4-ene-3,20-dione (13635-19-3)

Conditions	Yield
With toluene-4-sulfonic acid

17-alpha-Hydroxy-19-norprogesterone (2137-18-0) → 11β-hydroxy-estr-4-ene-3,17-dione (15313-96-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: mit Hilfe von Homogenaten aus Nebennieren 2: NaBiO3; aqueous acetic acid View Scheme
Multi-step reaction with 4 steps 1: THF; methanol; iodine / anschliessendes Behandeln mit wss.NaOH und Erwaermen des Reaktionsprodukts mit Kaliumacetat in Aceton 2: aqueous methanol.KHCO3 3: mit Hilfe von Homogenaten aus Nebennieren 4: NaBiO3; aqueous acetic acid View Scheme

17-alpha-Hydroxy-19-norprogesterone (2137-18-0) → 17,21-dihydroxy-19-nor-pregn-4-ene-3,20-dione (115184-02-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: THF; methanol; iodine / anschliessendes Behandeln mit wss.NaOH und Erwaermen des Reaktionsprodukts mit Kaliumacetat in Aceton 2: aqueous methanol.KHCO3 View Scheme

17-alpha-Hydroxy-19-norprogesterone (2137-18-0) → 17,21-dihydroxy-19-nor-pregn-4-ene-3,11,20-trione (111901-74-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: mit Hilfe von Homogenaten aus Nebennieren 2: CrO3; acetic acid View Scheme
Multi-step reaction with 4 steps 1: THF; methanol; iodine / anschliessendes Behandeln mit wss.NaOH und Erwaermen des Reaktionsprodukts mit Kaliumacetat in Aceton 2: aqueous methanol.KHCO3 3: mit Hilfe von Homogenaten aus Nebennieren 4: CrO3; acetic acid View Scheme

kieselguhr + dipropoxymethane (505-84-0) + 17-alpha-Hydroxy-19-norprogesterone (2137-18-0) → 17α-propoxymethoxy-19-nor-4-pregnene-3,20-dione

Conditions	Yield
With phosphorus pentaoxide In dichloromethane

kieselguhr + formaldehyde diethyl acetal (462-95-3) + 17-alpha-Hydroxy-19-norprogesterone (2137-18-0) → 17α-ethoxymethoxy-19-nor-4-pregnene-3,20-dione

Conditions	Yield
With phosphorus pentaoxide In dichloromethane

17-alpha-Hydroxy-19-norprogesterone (2137-18-0) → 17α-methoxymethoxy-19-nor-4-pregnene-3,20-dione

Conditions	Yield
In Dimethoxymethane

17-alpha-Hydroxy-19-norprogesterone (2137-18-0) → 3-ethoxy-17α-acetoxy-19-norpregna-3,5-diene-20-one

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / 24 h / 20 °C 2: toluene-4-sulfonic acid / tetrahydrofuran / 24 h / 20 °C View Scheme

17-alpha-Hydroxy-19-norprogesterone (2137-18-0) → 6-formyl-3-ethoxy-17α-acetoxy-19-norpregna-3,5-diene-20-one (147508-40-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / 24 h / 20 °C 2: toluene-4-sulfonic acid / tetrahydrofuran / 24 h / 20 °C 3: trichlorophosphate / -10 °C View Scheme

17-alpha-Hydroxy-19-norprogesterone (2137-18-0) → 17α-acetoxy-6-methylene-19-norpregn-4-ene-3,20-dione (58652-19-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / 24 h / 20 °C 2: toluene-4-sulfonic acid / tetrahydrofuran / 24 h / 20 °C 3: trichlorophosphate / -10 °C 4: sodium tetrahydroborate / methanol / 20 °C View Scheme

17-alpha-Hydroxy-19-norprogesterone (2137-18-0) → nomegestrol acetate (58652-20-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: toluene-4-sulfonic acid / 24 h / 20 °C 2: toluene-4-sulfonic acid / tetrahydrofuran / 24 h / 20 °C 3: trichlorophosphate / -10 °C 4: sodium tetrahydroborate / methanol / 20 °C 5: 5%-palladium/activated carbon / ethanol; tetrahydrofuran / 0.75 h / Reflux View Scheme

Upstream product

• 734-32-7 estra-4-ene-3,17-dione 
• 17976-32-8 3-methoxyestra-2,5⁽¹⁰⁾-dien-17-one 
• 917-54-4 methyllithium 
• 72-33-3 mestranol 
• 1624-62-0 estrone 3-methyl ether 
• 53-16-7 Estrone 
• 14328-46-2 20,20-(ethylenedioxy)-3-methoxy-17α-hydroxy-19-norpregna-1,3,5(10)-triene 
• 111979-17-0 16α,17-epoxy-3-methoxy-19-nor-pregna-1,3,5(10)-trien-20-one 
• 67519-64-6 16α,17α-epoxy-17-acetyl-Δ^1,3,5(10)-estratriene 
• 101766-63-6 3-hydroxy-19-norpregna-1,3,5⁽¹⁰⁾,16-tetraen-20-one 
• 1624-58-4 17α-hydroxy-3-methoxy-19-norpregna-1,3,5(10)-trien-20-one 
• 14339-99-2 20,20-ethanediyldioxy-3-methoxy-19-nor-pregna-2,5⁽¹⁰⁾-dien-17-ol 

Downstream Products

• 1253-28-7 gestonorone caproate 
• 58652-19-0 17α-acetoxy-6-methylene-19-norpregn-4-ene-3,20-dione 
• 58652-20-3 nomegestrol acetate 
• 31981-44-9 17α-acetoxy-19-norpregna-4-ene-3,20-dione 
• 54947-44-3 11β,17,21-trihydroxy-19-nor-pregn-4-ene-3,20-dione 

Relevant articles and documents

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A PROCESS FOR THE PRODUCTION OF OF 19-NORPREGN-4-EN-3,20-DIONE-17.ALPHA.-OL (GESTONORONE) AND INTERMEDIATES THEREFOR

The present invention relates to a new stereoselective process for the synthesis of 17(α)-17-acetyl-17-hydroxy-estr-4-en-3-one of formula (I), as well as to the new intermediates of the process. The 17(α)-17-acetyl-17-hy droxy-estr-4-en-3 -one (gestonorone) is an important intermediate in the synthesis of the active ingredients having progestogen activity - such as gestonorone capronate and nomegestroi acetate. Formulas (I), (II) and (III).

Novel 17-esters of 17α-hydroxy gestogens, compositions containing such compounds, processes for their preparation and methods of treatment therewith

This invention relates to novel 17α-esters of gestogens having an antitumour activity and to the preparation thereof. The invention is also concerned with pharmaceutical compositions containing the said compounds, and method of treatment therewith.