3962-66-1

Basic information

• Product Name: 19-Norandrost-5(10)-ene-3,17-dione
• Synonyms: ESTRA-5-ENE-3,17-DIONE;ESTR-5(10)-ENE-3,17-DIONE;oestr-5(10)-ene-3,17-dione;Estra-5(10)-ene-3,17-dione;Estr-5-ene-3beta,17beta-dione;19-NOR-Androst-5(10)-ene-3,17-;ESTR-5(10)-EN-17SS-OL-3-ONE;Norandrost-5(10)-Ene-Dione
• CAS NO: 3962-66-1
• Molecular Formula: C₁₈H₂₄O₂
• Molecular Weight: 272.38
• EINECS: 223-564-1
• Product Categories: Steroids
• Mol File: 3962-66-1.mol
• Article Data: 6

Chemical Properties

• Melting Point: 144-146 °C
• Boiling Point: 427.5 °C at 760 mmHg
• Flash Point: 159.7 °C
• Appearance: /
• Density: 1.13 g/cm³
• Vapor Pressure: 1.63E-07mmHg at 25°C
• Refractive Index: 1.555
• Water Solubility: 24mg/L at 20℃
• CAS DataBase Reference: 19-Norandrost-5(10)-ene-3,17-dione(CAS DataBase Reference)
• NIST Chemistry Reference: 19-Norandrost-5(10)-ene-3,17-dione(3962-66-1)
• EPA Substance Registry System: 19-Norandrost-5(10)-ene-3,17-dione(3962-66-1)

Safety Data

• Hazardous Substances Data: 3962-66-1(Hazardous Substances Data)

Usage

Flammability and Explosibility

Nonflammable

InChI:InChI=1/C18H24O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h14-16H,2-10H2,1H3/t14-,15-,16+,18+/m1/s1

Synthetic route

androst-4-ene-3,17-dion-19-oic acid (4757-95-3) → estra-5(10)-en-3,17-dione (3962-66-1)

Conditions	Yield
With pyridine for 0.5h; Heating;	82%
In pyridine at 50℃; for 1h;	700 mg

19-oxoandrostenedione (968-49-0) → estra-5(10)-en-3,17-dione (3962-66-1) + (19S)-3-hydroxy-3β,19-oxido-5β,19-cycloandrostane-17-one + (19R)-19-hydroxy-5β,19-cycloandrostane-3,17-dione (160617-57-2) + (19S)-19-hydroxy-5β,19-cycloandrostane-3,17-dione (160617-58-3)

Conditions	Yield
With acetic acid; zinc for 1.5h; Title compound not separated from byproducts;	A 3.3% B n/a C 62.5% D n/a
With acetic acid; zinc for 1.5h;	A 3.3% B n/a C 62.5% D n/a

19-oxoandrostenedione (968-49-0) → 17β-hydroxy-estr-5(10)-en-3-one (1089-78-7) + estra-5(10)-en-3,17-dione (3962-66-1) + (19R)-19-hydroxy-5β,19-cycloandrostane-3,17-dione (160617-57-2) + (19R)-17β,19-dihydroxy-5β,19-cycloandrostan-3-one (192373-63-0)

Conditions	Yield
With ammonia; lithium In tetrahydrofuran for 0.5h;	A 12% B 11% C 11% D 34%

3-methoxyestra-2,5(10)-dien-17-one (17976-32-8) → estra-5(10)-en-3,17-dione (3962-66-1)

Conditions	Yield
With methanol; acetic acid

19-hydroxy-4-androstene-3,17-dione (510-64-5) → estra-5(10)-en-3,17-dione (3962-66-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 60 percent / pyridinium dichromate / CH2Cl2 / 18 h / 20 °C 2: 3.3 percent / Zn, 50percent aq. AcOH / 1.5 h View Scheme
Multi-step reaction with 2 steps 1: 7.3 g / Cr2O3, conc. H2SO4 / acetone / 0.5 h / 10 - 15 °C 2: 700 mg / pyridine / 1 h / 50 °C View Scheme

17,17-ethanediyldioxy-3-methoxy-estra-2,5(10)-diene (1238-30-8) → estra-5(10)-en-3,17-dione (3962-66-1)

Conditions	Yield
With malonic acid In water; acetone at 20℃; for 4h; Temperature; Reagent/catalyst;

Estrone (53-16-7) → estra-5(10)-en-3,17-dione (3962-66-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 16 h / 130 °C 2.1: orthoformic acid triethyl ester; boron trifluoride diethyl etherate / 0.25 h / 25 °C 2.2: 5 h / 25 °C 3.1: ammonia; sodium hydroxide; lithium / tetrahydrofuran / 0.5 h / -78 - -50 °C 3.2: 1 h 4.1: malonic acid / acetone; water / 4 h / 20 °C View Scheme

estrone 3-methyl ether (1624-62-0) → estra-5(10)-en-3,17-dione (3962-66-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: orthoformic acid triethyl ester; boron trifluoride diethyl etherate / 0.25 h / 25 °C 1.2: 5 h / 25 °C 2.1: ammonia; sodium hydroxide; lithium / tetrahydrofuran / 0.5 h / -78 - -50 °C 2.2: 1 h 3.1: malonic acid / acetone; water / 4 h / 20 °C View Scheme

17,17-ethylenedioxy-3-methoxyoestra-1,3,5(10)-triene (28336-29-0) → estra-5(10)-en-3,17-dione (3962-66-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: ammonia; sodium hydroxide; lithium / tetrahydrofuran / 0.5 h / -78 - -50 °C 1.2: 1 h 2.1: malonic acid / acetone; water / 4 h / 20 °C View Scheme

estra-5(10)-en-3,17-dione (3962-66-1) → 10β-hydroxy-19-norandrost-4-ene-3,17-dione (5189-96-8)

Conditions	Yield
With copper(II) bis(trifluoromethanesulfonate); triphenylphosphine; N,N,N',N'-tetramethylguanidine In tetrahydrofuran at 20℃; for 17h; regioselective reaction;	56%
(i) Na2CrO4, AcOH, (ii) SiO2; Multistep reaction;

Perbenzoic acid (93-59-4) + estra-5(10)-en-3,17-dione (3962-66-1) → 10β-hydroxy-19-norandrost-4-ene-3,17-dione (5189-96-8)

Conditions	Yield
With benzene

methanol (67-56-1) + estra-5(10)-en-3,17-dione (3962-66-1) → 3,3-dimethoxyestr-5(10)-en-17-one (19257-34-2)

Conditions	Yield
With malonic acid for 19h;	5.1 g

estra-5(10)-en-3,17-dione (3962-66-1) + ethylene glycol (107-21-1) → 3,3-(ethylenedioxy)-5(10)-estren-17-one (6193-99-3) + estr-5(10)-ene-3,17-dione bis(ethylene ketal) (2220-74-8)

Conditions	Yield
With toluene-4-sulfonic acid In benzene for 2h; Heating;	A 586 mg B 2.55 g

estra-5(10)-en-3,17-dione (3962-66-1) + ethylene glycol (107-21-1) → estr-5(10)-ene-3,17-dione bis(ethylene ketal) (2220-74-8)

Conditions	Yield
With toluene-4-sulfonic acid In benzene Heating; Yield given;

estra-5(10)-en-3,17-dione (3962-66-1) + Dimethyl chlorophosphate (813-77-4) → Phosphoric acid dimethyl ester (8R,9S,13S,14S)-13-methyl-17-oxo-2,6,7,8,9,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl ester (118544-10-8)

Conditions	Yield
With 2,2,6,6-tetramethyl-piperidine; n-butyllithium 1.) hexane, THF, -70 deg C, 15 min, to room temp.; 2.) HMPA, 5 min, room temp.; Yield given. Multistep reaction;

estra-5(10)-en-3,17-dione (3962-66-1) → 3β-Hydroxyestr-5(10)-en-17-one (3461-60-7)

Conditions	Yield
(enzymatic reduction);

estra-5(10)-en-3,17-dione (3962-66-1) → C18H24O3 + 3-keto-5,10β-epoxy-nor-19-methyl androstanone (5190-31-8)

Conditions	Yield
With dioxyphthalic acid In diethyl ether; chloroform for 2h; Title compound not separated from byproducts;

estra-5(10)-en-3,17-dione (3962-66-1) → estra-4-ene-3,17-dione (734-32-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 2.55 g / TsOH / benzene / 2 h / Heating 2: 1.) tBuOK, 2.) TsOH / 1.) Et2O, -30 deg C, 24 h, 2.) acetone, TsOH, 2 h View Scheme
Multi-step reaction with 2 steps 1: 2.55 g / TsOH / benzene / 2 h / Heating 2: 1.) tBuOK, CHBr3, 2.) TsOH / 1.) Et2O, -30 deg C, 24 h, 2.) acetone, TsOH, 2 h View Scheme
Multi-step reaction with 5 steps 1: p-TSA / benzene / Heating 2: N-bromosuccinimide, MgO, H2O / dimethylformamide / 2 h / Ambient temperature 3: 71 percent / NaOMe / methanol; tetrahydrofuran / 8 h / 4 °C 4: 71 percent / KHS, 18-crown-6 / ethane-1,2-diol / 2 h / 140 °C 5: 27 percent / p-TSA / acetone / Ambient temperature View Scheme

estra-5(10)-en-3,17-dione (3962-66-1) → 17β-((tert-Butyldimethylsilyl)oxy)estr-4-en-3-one (139042-19-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: 5.1 g / malonic acid / 19 h 2: 5.2 g / NaBH4 / methanol / 1 h 3: 1.7 g / imidazole / dimethylformamide / 1 h / 50 °C 4: 1.) aq. NaOH, BTEAC, CHCl3, 2.) TsOH / 1.) room temperature, 16 h, 2.) acetone, 30 min View Scheme
Multi-step reaction with 3 steps 1: 586 mg / TsOH / benzene / 2 h / Heating 2: 1.) NaBH4, 2.) imidazole / 1.) MeOH, 1 h, 2.) DMF, 50 deg C, 2 h 3: 1.) tBuOK, 2.) TsOH / 1.) Et2O, -30 deg C, 24 h, 2.) acetone, 2 h View Scheme
Multi-step reaction with 3 steps 1: 586 mg / TsOH / benzene / 2 h / Heating 2: 1.) NaBH4, 2.) imidazole / 1.) MeOH, 1 h, 2.) DMF, 50 deg C, 2 h 3: 1.) tBuOK, CHBr3, 2.) TsOH / 1.) Et2O, -30 deg C, 24 h, 2.) acetone, 2 h View Scheme

estra-5(10)-en-3,17-dione (3962-66-1) → 19(S)-bromo-9α,19-cyclo-10α-androst-4-ene-3,17-dione

Conditions	Yield
Multi-step reaction with 2 steps 1: 2.55 g / TsOH / benzene / 2 h / Heating 2: 1.) tBuOK, 2.) TsOH / 1.) Et2O, -30 deg C, 24 h, 2.) acetone, TsOH, 2 h View Scheme
Multi-step reaction with 2 steps 1: 2.55 g / TsOH / benzene / 2 h / Heating 2: 1.) tBuOK, CHBr3, 2.) TsOH / 1.) Et2O, -30 deg C, 24 h, 2.) acetone, TsOH, 2 h View Scheme

estra-5(10)-en-3,17-dione (3962-66-1) → 17β-hydroxy-19,19-dichloro-5α,19-cyclo-10α-androstan-3-one

Conditions	Yield
Multi-step reaction with 4 steps 1: 5.1 g / malonic acid / 19 h 2: 5.2 g / NaBH4 / methanol / 1 h 3: 1.7 g / imidazole / dimethylformamide / 1 h / 50 °C 4: 1.) aq. NaOH, BTEAC, CHCl3, 2.) TsOH / 1.) room temperature, 16 h, 2.) acetone, 30 min View Scheme

estra-5(10)-en-3,17-dione (3962-66-1) → tert-Butyl-((8R,9S,13S,14S,17S)-3,3-dimethoxy-13-methyl-2,3,4,6,7,8,9,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yloxy)-dimethyl-silane (158388-33-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 5.1 g / malonic acid / 19 h 2: 5.2 g / NaBH4 / methanol / 1 h 3: 1.7 g / imidazole / dimethylformamide / 1 h / 50 °C View Scheme

estra-5(10)-en-3,17-dione (3962-66-1) → 17β-(tert-butyldimethylsiloxy)-3,3-ethylenedioxyestr-5(10)-ene (158388-29-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 586 mg / TsOH / benzene / 2 h / Heating 2: 1.) NaBH4, 2.) imidazole / 1.) MeOH, 1 h, 2.) DMF, 50 deg C, 2 h View Scheme

estra-5(10)-en-3,17-dione (3962-66-1) → 17β-(tert-butyldimethylsiloxy)-19,19-dibromo-5,19-cyclo-10α-androstan-3-one

Conditions	Yield
Multi-step reaction with 4 steps 1: 5.1 g / malonic acid / 19 h 2: 5.2 g / NaBH4 / methanol / 1 h 3: 1.7 g / imidazole / dimethylformamide / 1 h / 50 °C 4: 1.) CTAB, aq. NaOH, 2.) TsOH / 1.) 48 h, 2.) acetone, 1 h View Scheme

estra-5(10)-en-3,17-dione (3962-66-1) → 17β-(tert-butyldimethylsiloxy)-19(S)-chloro-5α-hydroxy-9α,19-cyclo-10α-androstan-3-one

Conditions	Yield
Multi-step reaction with 4 steps 1: 5.1 g / malonic acid / 19 h 2: 5.2 g / NaBH4 / methanol / 1 h 3: 1.7 g / imidazole / dimethylformamide / 1 h / 50 °C 4: 1.) aq. NaOH, BTEAC, CHCl3, 2.) TsOH / 1.) room temperature, 16 h, 2.) acetone, 30 min View Scheme

estra-5(10)-en-3,17-dione (3962-66-1) → 19(S)-bromo-17β-(tert-butyldimethylsiloxy)-9α,19-cyclo-10α-androst-4-en-3-one

Conditions	Yield
Multi-step reaction with 4 steps 1: 5.1 g / malonic acid / 19 h 2: 5.2 g / NaBH4 / methanol / 1 h 3: 1.7 g / imidazole / dimethylformamide / 1 h / 50 °C 4: 1.) CTAB, aq. NaOH, 2.) aq. HCl / 1.) 18 h, 2.) acetone, 30 min View Scheme
Multi-step reaction with 3 steps 1: 586 mg / TsOH / benzene / 2 h / Heating 2: 1.) NaBH4, 2.) imidazole / 1.) MeOH, 1 h, 2.) DMF, 50 deg C, 2 h 3: 1.) tBuOK, 2.) TsOH / 1.) Et2O, -30 deg C, 24 h, 2.) acetone, 2 h View Scheme
Multi-step reaction with 3 steps 1: 586 mg / TsOH / benzene / 2 h / Heating 2: 1.) NaBH4, 2.) imidazole / 1.) MeOH, 1 h, 2.) DMF, 50 deg C, 2 h 3: 1.) tBuOK, CHBr3, 2.) TsOH / 1.) Et2O, -30 deg C, 24 h, 2.) acetone, 2 h View Scheme

estra-5(10)-en-3,17-dione (3962-66-1) → 17β-(tertbutyldimethylsiloxy)-9α-dichloromethylandrost-5(10)-en-3-one

Conditions	Yield
Multi-step reaction with 4 steps 1: 5.1 g / malonic acid / 19 h 2: 5.2 g / NaBH4 / methanol / 1 h 3: 1.7 g / imidazole / dimethylformamide / 1 h / 50 °C 4: 1.) aq. NaOH, BTEAC, CHCl3, 2.) TsOH / 1.) room temperature, 16 h, 2.) acetone, 30 min View Scheme

estra-5(10)-en-3,17-dione (3962-66-1) → 19(S)-bromo-17β-(tert-butyldimethylsiloxy)-5β,6β-dibromomethylene-3,3-dimethoxy-9α,19-cyclo-10α-androst-5(10)-ene

Conditions	Yield
Multi-step reaction with 4 steps 1: 5.1 g / malonic acid / 19 h 2: 5.2 g / NaBH4 / methanol / 1 h 3: 1.7 g / imidazole / dimethylformamide / 1 h / 50 °C 4: 650 mg / CTAB, aq. NaOH / 18 h / Ambient temperature View Scheme

estra-5(10)-en-3,17-dione (3962-66-1) → 17β-(tert-butyldimethylsiloxy)-19(S)-chloro-5β,6β-dichloromethylene-3,3-ethylenedioxy-9α,19-cyclo-10α-androstane

Conditions	Yield
Multi-step reaction with 3 steps 1: 586 mg / TsOH / benzene / 2 h / Heating 2: 1.) NaBH4, 2.) imidazole / 1.) MeOH, 1 h, 2.) DMF, 50 deg C, 2 h 3: 41 mg / various solvent(s) / 3.5 h / 120 - 130 °C View Scheme

estra-5(10)-en-3,17-dione (3962-66-1) → 19(S)-bromo-17β-(tert-butyldimethylsiloxy)-5β,6β-dibromomethylene-3,3-ethylenedioxy-9α,19-cyclo-10α-androstane

Conditions	Yield
Multi-step reaction with 3 steps 1: 586 mg / TsOH / benzene / 2 h / Heating 2: 1.) NaBH4, 2.) imidazole / 1.) MeOH, 1 h, 2.) DMF, 50 deg C, 2 h 3: 1.) aq. NaOH, CTAB, 2.) TsOH / 1.) 18 h, 2.) acetone View Scheme

estra-5(10)-en-3,17-dione (3962-66-1) → 19(S)-bromo-17β-(tert-butyldimethylsiloxy)-5β,6β-dibromomethylene-9α,19-cyclo-10α-androstan-3-one (158388-34-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: 5.1 g / malonic acid / 19 h 2: 5.2 g / NaBH4 / methanol / 1 h 3: 1.7 g / imidazole / dimethylformamide / 1 h / 50 °C 4: 1.) CTAB, aq. NaOH, 2.) TsOH / 1.) 48 h, 2.) acetone, 1 h View Scheme
Multi-step reaction with 4 steps 1: 5.1 g / malonic acid / 19 h 2: 5.2 g / NaBH4 / methanol / 1 h 3: 1.7 g / imidazole / dimethylformamide / 1 h / 50 °C 4: 1.) CTAB, aq. NaOH, 2.) aq. HCl / 1.) 18 h, 2.) acetone, 30 min View Scheme
Multi-step reaction with 5 steps 1: 5.1 g / malonic acid / 19 h 2: 5.2 g / NaBH4 / methanol / 1 h 3: 1.7 g / imidazole / dimethylformamide / 1 h / 50 °C 4: 650 mg / CTAB, aq. NaOH / 18 h / Ambient temperature 5: 200 mg / aq. HCl / acetone / 0.5 h / Ambient temperature View Scheme

estra-5(10)-en-3,17-dione (3962-66-1) → 3,3-dimethoxyestr-5(10)-en-17β-ol (56016-36-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 5.1 g / malonic acid / 19 h 2: 5.2 g / NaBH4 / methanol / 1 h View Scheme

Upstream product

• 1238-30-8 17,17-ethanediyldioxy-3-methoxy-estra-2,5⁽¹⁰⁾-diene 
• 53-16-7 Estrone 
• 1624-62-0 estrone 3-methyl ether 
• 28336-29-0 17,17-ethylenedioxy-3-methoxyoestra-1,3,5⁽¹⁰⁾-triene 
• 510-64-5 19-hydroxy-4-androstene-3,17-dione 
• 4757-95-3 androst-4-ene-3,17-dion-19-oic acid 
• 17976-32-8 3-methoxyestra-2,5⁽¹⁰⁾-dien-17-one 
• 968-49-0 19-oxoandrostenedione 

Downstream Products

• 19257-34-2 3,3-dimethoxyestr-5(10)-en-17-one 
• 6193-99-3 3,3-(ethylenedioxy)-5(10)-estren-17-one 
• 2220-74-8 estr-5⁽¹⁰⁾-ene-3,17-dione bis(ethylene ketal) 
• 5190-31-8 3-keto-5,10β-epoxy-nor-19-methyl androstanone 
• 734-32-7 estra-4-ene-3,17-dione 
• 56016-36-5 3,3-dimethoxyestr-5(10)-en-17β-ol 
• 77016-85-4 10β-(2-propynyl)estr-4-ene-3,17-dione 
• 4993-32-2 estr-5(10)-ene-3β,17β-diol 
• 13864-49-8 5(10)-estrene-3α,17β-diol 

Relevant articles and documents

Preparation 19-nor -5 (10)-androstene ketone compound method

The invention discloses a method for preparing a 19-Norandrost-5(10)-ene-3,17-dione compound. The method comprises the steps of by taking estrone as an ingredient, firstly sequentially performing etherification reaction, ketal protection reaction and birch reduction reaction to obtain a birch reduction product; then by taking lower fatty acid as a catalyst, performing selective hydrolysis reaction on the birch reduction product to produce the 19-Norandrost-5(10)-ene-3,17-dione compound. According to the method, the hydrolysis technology of the birch reduction product containing 17-bit ketal protecting group is optimized and improved, and the single 19-Norandrost-5(10)-ene-3,17-dione with high yield and high selectivity can be obtained through selective hydrolysis reaction by taking binary fatty acid as an acid catalyst for the first time; in addition, the fact that the 17-bit ketal protecting derivatives of the single 19-Norandrost-5(10)-ene-3,17-dione compound can be obtained by taking lower unitary fatty acid as a catalyst is found for the first time.

Novel Insertion, Rearrangement and Addition Products from Dihalogenocarbene Reactions with 5(10)-Unsaturated Steroids

Novel insertion, rearrangement and addition products from dibromocarbene and dichlorocarbene reactions with 5(10)-unsaturated steroids have been identified.The dihalogenocarbenes were prepared under phase-transfer conditions (CHBr3- or CHCl3-NaOH), and from CHBr3-KOBut-Et2O, phenyl(trichloromethyl)mercury and sodium trichloroacetate.Evidence that the major products arise from an initial dihalogenocarbene reaction on the α face of the molecule is reported.The major products obtained from addition of CBr2 to 3,17-disubstituted estr-5(10)-enes, after ketal hydrolysis, were 19(S)-bromo-9α,19-cyclo-10α-androst-4-en-3-one and 3',3',19(S)-tribromo-3'H-9α,19-cyclopropa-5β,10α-androstan-3-one derivatives together with the 19,19-dibromo-5α,19-cyclo-10α-steroid adduct.No products from addition of CBr2 to the β-face of the double bond, as previously reported, were identified.Reactions of CCl2 gave, besides rearrangement products analogous to those obtained from CBr2, a 5α-hydroxy-9α,19α-cycloandrostane derivative, the 9α-CHCl2 insertion derivative and both α- and β-face addition products to the double bond.Structures were established by homonuclear and heteronuclear correlation and nuclear Overhauser effect NMR measurements and X-ray crystallography.

Suicide inhibitors of aromatase

Thiol-substituted synthetic steriod hormones or androgens having a testosterone ring system backbone are used to inhibit aromatase''s catalyzed conversion of C 19 androgens having a A 4,3-ketone group to estrogens in the treatment of estrogen-dependent tumors, such as metastatic breast cancer in postmenopausal females.The compounds have the general formula: STR1 wherein R 1 =a thiol, such as --SH or --CH 2 SH, and R 2 =OH or =O. The preferred synthetic hormones are 17β-hydroxy-10β-mercaptoestr-4-en-3-one, 19-mercaptoandrost-4-en-3,17-dione, and 10β-mercaptoandrost-4-en-3,17-dione.