126690-41-3

Basic information

• Product Name: (5a,11b)-11-[4-(Dimethylamino)phenyl]-5,17-dihydroxy-19-norpregn-9-ene-3,20-dione cyclic bis(1,2-ethanediyl acetal)
• Synonyms: (5a,11b)-11-[4-(Dimethylamino)phenyl]-5,17-dihydroxy-19-norpregn-9-ene-3,20-dione cyclic bis(1,2-ethanediyl acetal);3,3,3,20,20-Bis(ethylene-dioxy) -5α,17α-dihydroxy-11β-[4-(N, N-diMethylaMino)-phenyl]-19-norpregna-9(11)-ene;3,3,3,20,20-Bis(ethylene-dioxy) -5alpha,17alpha-dihydroxy-11beta-[4-(N, N-diMethylaMino)-phenyl]-19-norpregna-9(11)-ene;3,3,20,20-Bis(ethylene-dioxy) -5α, 17α-dihydroxy-11β- 4-(N,N-diMethylaMino) -phenyl -19-norpregna-9(11)-ene;(5alpha,11beta)-11-[4-(Dimethylamino)phenyl]-5,17-dihydroxy-19-norpregn-9-ene-3,20-dione cyclic bis(1,2-ethanediyl acetal);3,20-bis-ethylenedioxy-5,17-dihydroxy-11-(4-N,N-dimethylaminophenyl)-19-norpregn-9-ene;(5α,11β)-11-[4-(Dimethylamino)phenyl]-5,17-dihydroxy-19-norpregn-9-ene-3,20-dione cyclicbis(1,2-ethanediyl acetal)
• CAS NO: 126690-41-3
• Molecular Formula: C₃₂H₄₅NO₆
• Molecular Weight: 539.7
• EINECS: 1592732-453-0
• Mol File: 126690-41-3.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 697.0±55.0 °C(Predicted)
• Appearance: /
• Density: 1.27
• PKA: 14.69±0.70(Predicted)
• CAS DataBase Reference: (5a,11b)-11-[4-(Dimethylamino)phenyl]-5,17-dihydroxy-19-norpregn-9-ene-3,20-dione cyclic bis(1,2-ethanediyl acetal)(CAS DataBase Reference)
• NIST Chemistry Reference: (5a,11b)-11-[4-(Dimethylamino)phenyl]-5,17-dihydroxy-19-norpregn-9-ene-3,20-dione cyclic bis(1,2-ethanediyl acetal)(126690-41-3)
• EPA Substance Registry System: (5a,11b)-11-[4-(Dimethylamino)phenyl]-5,17-dihydroxy-19-norpregn-9-ene-3,20-dione cyclic bis(1,2-ethanediyl acetal)(126690-41-3)

Safety Data

• Hazardous Substances Data: 126690-41-3(Hazardous Substances Data)

Usage

General Description

The chemical "(5a,11b)-11-[4-(Dimethylamino)phenyl]-5,17-dihydroxy-19-norpregn-9-ene-3,20-dione cyclic bis(1,2-ethanediyl acetal)" is a complex organic compound with a steroid-like structure. It contains a norpregnane skeleton and two cyclic bis(1,2-ethanediyl acetal) groups. The molecule also features a dimethylamino-phenyl group and multiple hydroxyl groups. (5a,11b)-11-[4-(Dimethylamino)phenyl]-5,17-dihydroxy-19-norpregn-9-ene-3,20-dione cyclic bis(1,2-ethanediyl acetal) may have potential applications in the pharmaceutical industry, particularly in the development of hormone-based medications or other drugs targeting specific biological pathways. Its unique structure and functional groups make it a potentially interesting molecule for further research and development.

Synthetic route

3,3,20,20-bis(ethylenedioxy)-17α-hydroxy-5α,10α-epoxy-19-norpregna-9(11)-ene + 4-dimethylaminophenylmagnesium bromide (7353-91-5) → 3,3,20,20-bis(ethylene-dioxy)-5α-17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl-]-19-norpregna-9(11)-ene (126690-41-3)

Conditions	Yield
With copper(l) iodide; dimethylsulfide In tetrahydrofuran at 20℃;	93%

4-bromo-N,N-dimethylaniline (586-77-6) + 5α,10α-epoxy-17α-hydroxy-19-norpregn-9(11)-ene-3,20-dione 3,20-bis(ethylene acetal) (54201-83-1) → 3,3,20,20-bis(ethylene-dioxy)-5α-17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl-]-19-norpregna-9(11)-ene (126690-41-3)

Conditions	Yield
Stage #1: 4-bromo-N,N-dimethylaniline With 1,1-Dibromoethane; iodine; magnesium In tetrahydrofuran for 1.5h; Stage #2: 5α,10α-epoxy-17α-hydroxy-19-norpregn-9(11)-ene-3,20-dione 3,20-bis(ethylene acetal) With copper(l) chloride In tetrahydrofuran at 20℃; for 1h; Grignard reaction;	76%

3,3,20,20-bis(ethylene-dioxy)-17α-hydroxy-5,10-epoxy-19-norpregn-9(11)-ene → 3,3,20,20-bis(ethylene-dioxy)-5α-17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl-]-19-norpregna-9(11)-ene (126690-41-3)

Conditions	Yield
Stage #1: 4-bromo-N,N-dimethylaniline With magnesium; ethylene dibromide In tetrahydrofuran at 15 - 50℃; for 2.08333h; Stage #2: 3,3,20,20-bis(ethylene-dioxy)-17α-hydroxy-5,10-epoxy-19-norpregn-9(11)-ene; copper(l) chloride In tetrahydrofuran; dichloromethane at 15 - 25℃; for 2.75h; Stage #3: With water; ammonium chloride In tetrahydrofuran; dichloromethane Product distribution / selectivity;	46%

17α-hydroxy-19-norpregna-5(10),9(11)-diene-3,20-dione 3,20-bis(ethylene acetal) (54201-84-2) → 3,3,20,20-bis(ethylene-dioxy)-5α-17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl-]-19-norpregna-9(11)-ene (126690-41-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 54.3 percent / 30 percent H2O2; (CF3)2CO*3H2O; Na2HPO4 / CH2Cl2 / 7.5 h / 4 °C 2.1: Mg; I2; dibromoethane / tetrahydrofuran / 1.5 h 2.2: 76 percent / CuCl / tetrahydrofuran / 1 h / 20 °C View Scheme

3,3-(ethylene-dioxy)-17β-cyano-17α-hydroxy-19-norpregna-5(10),9(11)-diene → 3,3,20,20-bis(ethylene-dioxy)-5α-17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl-]-19-norpregna-9(11)-ene (126690-41-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 98 percent / DMAP; TEA / tetrahydrofuran / 20 °C 2.1: Li; di-t-butyl biphenyl / tetrahydrofuran / 2.25 h / -70 °C 2.2: HC(OEt)3; p-TsOH / CH2Cl2 / 20 °C 3.1: 54.3 percent / 30 percent H2O2; (CF3)2CO*3H2O; Na2HPO4 / CH2Cl2 / 7.5 h / 4 °C 4.1: Mg; I2; dibromoethane / tetrahydrofuran / 1.5 h 4.2: 76 percent / CuCl / tetrahydrofuran / 1 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: dmap; triethylamine / tetrahydrofuran / 12 h / 5 - 20 °C 2.1: copper(I) bromide / tetrahydrofuran; toluene / 23 h / 20 °C 3.1: orthoformic acid triethyl ester; toluene-4-sulfonic acid / dichloromethane / 18 h / 20 °C 3.2: 0.42 h / 4 °C 4.1: copper(l) iodide; dimethylsulfide / tetrahydrofuran / 20 °C View Scheme

3,3-ethylenedioxy-17β-cyano-17α-chloromethyl(dimethyl)siloxy estren-5(10),9(11)diene (290825-36-4) → 3,3,20,20-bis(ethylene-dioxy)-5α-17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl-]-19-norpregna-9(11)-ene (126690-41-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: Li; di-t-butyl biphenyl / tetrahydrofuran / 2.25 h / -70 °C 1.2: HC(OEt)3; p-TsOH / CH2Cl2 / 20 °C 2.1: 54.3 percent / 30 percent H2O2; (CF3)2CO*3H2O; Na2HPO4 / CH2Cl2 / 7.5 h / 4 °C 3.1: Mg; I2; dibromoethane / tetrahydrofuran / 1.5 h 3.2: 76 percent / CuCl / tetrahydrofuran / 1 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: copper(I) bromide / tetrahydrofuran; toluene / 23 h / 20 °C 2.1: orthoformic acid triethyl ester; toluene-4-sulfonic acid / dichloromethane / 18 h / 20 °C 2.2: 0.42 h / 4 °C 3.1: copper(l) iodide; dimethylsulfide / tetrahydrofuran / 20 °C View Scheme

4-bromo-N,N-dimethylaniline (586-77-6) + 3,3,20,20-bis(ethylene-dioxy)-17α-hydroxy-5β,10β-epoxy-19-norpregna-9(11)-ene → 3,3,20,20-bis(ethylene-dioxy)-5α-17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl-]-19-norpregna-9(11)-ene (126690-41-3)

Conditions	Yield
Stage #1: 4-bromo-N,N-dimethylaniline With magnesium In tetrahydrofuran; dichloromethane at 40 - 50℃; for 3h; Large scale; Stage #2: 3,3,20,20-bis(ethylene-dioxy)-17α-hydroxy-5β,10β-epoxy-19-norpregna-9(11)-ene With copper(l) chloride In tetrahydrofuran; dichloromethane at 10 - 20℃; for 2h; Cooling with ice; Large scale;	957g

4-bromo-N,N-dimethylaniline (586-77-6) + C24H34O6 → 3,3,20,20-bis(ethylene-dioxy)-5α-17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl-]-19-norpregna-9(11)-ene (126690-41-3)

Conditions	Yield
With magnesium; copper dichloride In tetrahydrofuran; ethylene dibromide at 10 - 25℃; for 2.5h;

C24H34O5 → 3,3,20,20-bis(ethylene-dioxy)-5α-17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl-]-19-norpregna-9(11)-ene (126690-41-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: dihydrogen peroxide; pyridine; 1,1,1,3,3,3-hexafluoro-2-propanone trihydrate / dichloromethane / -10 - 5 °C 2: magnesium; copper dichloride / tetrahydrofuran; ethylene dibromide / 2.5 h / 10 - 25 °C View Scheme

3,3,20,20-bis(ethylene-dioxy)-5α-17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl-]-19-norpregna-9(11)-ene (126690-41-3) → CDB-3236 (159811-51-5)

Conditions	Yield
With sulfuric acid In ethanol for 1h; Heating;	88%
Stage #1: 3,3,20,20-bis(ethylene-dioxy)-5α-17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl-]-19-norpregna-9(11)-ene With potassium hydrogensulfate; water at 5℃; for 4h; Stage #2: With potassium hydroxide; water In dichloromethane Product distribution / selectivity;
With hydrogenchloride; water at 25℃; for 2h;
With hydrogenchloride In water at 25℃; for 2h;

propionic acid (802294-64-0) + 3,3,20,20-bis(ethylene-dioxy)-5α-17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl-]-19-norpregna-9(11)-ene (126690-41-3) → 11β-[4-(N,N-dimethylamino)phenyl]-17α-propionyloxy-19-norpregna-4,9-diene-3,10-dione

Conditions	Yield
With toluene-4-sulfonic acid; trifluoroacetic anhydride In dichloromethane; water at 0℃; for 1h;	47%

3,3,20,20-bis(ethylene-dioxy)-5α-17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl-]-19-norpregna-9(11)-ene (126690-41-3) → ulipristal acetate (126784-99-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 88 percent / aq. H2SO4 / ethanol / 1 h / Heating 2: 68 percent / p-TsOH / CH2Cl2 / 0.33 h / 0 °C View Scheme

acetic anhydride (108-24-7) + 3,3,20,20-bis(ethylene-dioxy)-5α-17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl-]-19-norpregna-9(11)-ene (126690-41-3) → ulipristal acetate (126784-99-4)

Conditions	Yield
With perchloric acid; acetic acid In dichloromethane at -10 - 0℃; for 0.5h; Cooling with ice;

Upstream product

• 7353-91-5 4-dimethylaminophenylmagnesium bromide 
• 586-77-6 4-bromo-N,N-dimethylaniline 
• 290825-36-4 3,3-ethylenedioxy-17β-cyano-17α-chloromethyl(dimethyl)siloxy estren-5(10),9(11)diene 
• 54201-84-2 17α-hydroxy-19-norpregna-5(10),9(11)-diene-3,20-dione 3,20-bis(ethylene acetal) 
• 54201-83-1 5α,10α-epoxy-17α-hydroxy-19-norpregn-9(11)-ene-3,20-dione 3,20-bis(ethylene acetal) 

Downstream Products

• 126784-99-4 ulipristal acetate 
• 159811-51-5 CDB-3236 

Relevant articles and documents

A practical large-scale synthesis of 17α-acetoxy-11β-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione (CDB-2914)

A new practical synthesis of 17α-acetoxy-11β-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione (CDB-2914) is described. The synthesis gives easily isolable solids at all steps and is amenable to large-scale process. Copyright (C) 2000 Elsevier Science Inc.

Ulipristal acetate impurities and preparation and detection method thereof

The invention provides ulipristal acetate impurity compounds and a preparation method thereof, and particularly provides novel compound impurities including A (a compound A), G (a compound G), H (a compound H) and J (a compound J). The invention further provides a detection method of the impurities and application of the impurities on quality analysis of an ulipristal acetate bulk drug and a preparation thereof.

INDUSTRIAL PROCESS FOR THE SYNTHESIS OF 17α-ACETOXY-11β-[4-(N,N-DIMETHYL-AMINO)- PHENYL]-19-NORPREGNA-4,9-DIENE-3,20-DIONE AND NEW INTERMEDIATES OF THE PROCESS

The present invention relates to a new industrial process for the synthesis of solvate- free 17α-acetoxy-11β-[4-(N,N-dimethyl-amino)-phenyl]-19-norpregna-4,9-diene-3,20-dione [CDB -2914] of formula (I) which is a strong antiprogestogene and antiglucocorticoid agent. The invention also relates to compounds of formula (VII) and (VIII) used as intermediates in the process. The process according to the invention is the following: i) 3-(ethylene-dioxy)-estra-5(10),9(11)-diene-17-one of formula (X) is reacted with potassium acetilyde formed in situ in dry tetrahydrofuran by known method, ii) the obtained 3-(ethylene-dioxy)-17α-ethynyl-17β-hydroxy-estra-5(10),9(11)-diene of formula (IX) is reacted with phenylsulfenyl chloride in dichloromethane in the presence of triethylamine and acetic acid, iii) the obtained isomeric mixture of 3-(ethylene-dioxy)-21-(phenyl-sulfinyl)-19-norpregna-5(10),9(11),17(20),20-tetraene of formula (VIII) is reacted first with sodium methoxide in methanol, then with trimethyl phosphite, iv) the obtained 3-(ethylene-dioxy)-17α-hydroxy-20-methoxy-19-norpregna-5(10),9(11),20-triene of formula (VII) is reacted with hydrogen chloride in methanol, then v) the obtained 3-(ethylene-dioxy)-17α-hydroxy-19-norpregna-5(10),9(11l)-diene-20- one of formula (VI) is reacted with ethylene glycol hi dichloromethane in the presence of trimethyl orthoformate and p-toluenesulfonic acid by known method, vi) the obtained 3,3,20,20-bis(ethylene-dioxy)-17α-hydroxy-19-norpregna- 5(10),9(11)-diene of formula (V) is reacted with hydrogen peroxide in a mixture of pyridine and dichloromethane in the presence of hexachloroacetone by known method, vii) the obtained 3,3,20,20-bis(ethylene-dioxy)-17α-hydroxy-5,10-epoxy-19-norpregn-9(11)-ene of formula (IV), containing approximately a 1:1 mixture of 5α,10α- and 5β,10β-epoxides, is isolated from the solution and reacted with a Grignard reagent obtained from 4-bromo-N,N-dimethyl-aniline in tetrahydrofuran in the presence of copper(I) chloride catalyst without separation of the isomers by known method, viii) the obtained 3,3,20,20-bis(ethylene-dioxy)-5α,17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl]-19-norpregn-9(11)-ene of formula (III) is reacted with potassium hydrogensulfate in water by known method, ix) the obtained 11β-[4-(N,N-dimethylamino)-phenyl]-17α-hydroxy-19-norpregn-4,9-diene-3,20-dione of formula (II) is acetylated with acetic anhydride in the presence of perchloric acid by known method, finally x) the solvate-free compound of formula (I) is liberated from the obtained solvate containing compound of formula (I) in a 1 : 1 mixture of ethanol and water at 70° C.