159811-51-5

Usage

Uses

Used in Pharmaceutical Industry:
Ulipristal is used as a pharmaceutical agent for managing certain conditions during pregnancy. As a selective progesterone receptor modulator, it plays a crucial role in regulating hormonal balance and addressing specific medical needs related to pregnancy.
Used in Obstetrics and Gynecology:
In the field of obstetrics and gynecology, Ulipristal is utilized for its ability to modulate progesterone receptor activity. This makes it a valuable tool in the treatment of various pregnancy-related conditions, such as uterine fibroids and endometriosis, where hormonal regulation is essential for effective management.
Used in Clinical Research:
Ulipristal's unique properties as a selective progesterone receptor modulator also make it a subject of interest in clinical research. Scientists and medical professionals are exploring its potential applications in the development of new treatments for various reproductive health conditions, further expanding its use in the medical field.

Synthetic route

C31H43NO4 → CDB-3236 (159811-51-5)

Conditions	Yield
With hydrogenchloride In methanol; water at 20℃; for 1h; Industrial scale;	98.2%

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

11β-(4-N,N-dimethylaminophenyl)-17α-hydroxy-20-methoxy-19-norpregna-4,9,20-triene-3-one → CDB-3236 (159811-51-5)

Conditions	Yield
With acetic acid In water at 25℃; for 1h;	74%
With hydrogenchloride In methanol at 20℃; for 0.5h;	70%

11β-[4-(N,N-dimethylamino)phenyl]-3,3-ethylenedioxy-5,17α-bis[(trimethylsilyl)oxy]-5α-estr-9-en-17β-carbonitrile (1094602-02-4) + methyllithium (917-54-4) → CDB-3236 (159811-51-5)

Conditions	Yield
Stage #1: 11β-[4-(N,N-dimethylamino)phenyl]-3,3-ethylenedioxy-5,17α-bis[(trimethylsilyl)oxy]-5α-estr-9-en-17β-carbonitrile; methyllithium With N,N,N,N,-tetramethylethylenediamine at -50 - -35℃; for 3h; Stage #2: With water at 20℃; Stage #3: With sulfuric acid In methanol at 40℃; for 3h;	70.7%

11β-[4-(N,N-dimethylamino)phenyl]-3,3-ethylenedioxy-5α-hydroxy-17α-[(trimethylsilyl)oxy]-5α-estr-9-en-17β-carbonitrile (91934-94-0) + methyllithium (917-54-4) → CDB-3236 (159811-51-5)

Conditions	Yield
Stage #1: 11β-[4-(N,N-dimethylamino)phenyl]-3,3-ethylenedioxy-5α-hydroxy-17α-[(trimethylsilyl)oxy]-5α-estr-9-en-17β-carbonitrile; methyllithium With N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -50 - -40℃; for 3h; Stage #2: With water In tetrahydrofuran at 20℃; Stage #3: With sulfuric acid In methanol at 40℃; for 3h;	70%

17α-hydroxy-19-norpregna-5(10),9(11)-diene-3,20-dione 3,20-bis(ethylene acetal) (54201-84-2) → CDB-3236 (159811-51-5)

Conditions	Yield
Multi-step reaction with 3 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 3.1: 88 percent / aq. H2SO4 / ethanol / 1 h / Heating View Scheme
Multi-step reaction with 3 steps 1.1: Hexafluoroacetone; dihydrogen peroxide / dichloromethane; pyridine / -5 - 5 °C / Large scale 2.1: magnesium; copper(l) chloride / tetrahydrofuran / 3 h / 25 - 50 °C / Large scale 2.2: 2 h / 10 - 20 °C / Large scale 3.1: hydrogenchloride / 2 h / 25 °C View Scheme

5α,10α-epoxy-17α-hydroxy-19-norpregn-9(11)-ene-3,20-dione 3,20-bis(ethylene acetal) (54201-83-1) → CDB-3236 (159811-51-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: Mg; I2; dibromoethane / tetrahydrofuran / 1.5 h 1.2: 76 percent / CuCl / tetrahydrofuran / 1 h / 20 °C 2.1: 88 percent / aq. H2SO4 / ethanol / 1 h / Heating View Scheme
Multi-step reaction with 2 steps 1.1: magnesium; copper(l) chloride / tetrahydrofuran / 3 h / 25 - 50 °C / Large scale 1.2: 2 h / 10 - 20 °C / Large scale 2.1: hydrogenchloride / 2 h / 25 °C View Scheme

3,3-(ethylene-dioxy)-17β-cyano-17α-hydroxy-19-norpregna-5(10),9(11)-diene → CDB-3236 (159811-51-5)

Conditions	Yield
Multi-step reaction with 5 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 5.1: 88 percent / aq. H2SO4 / ethanol / 1 h / Heating View Scheme
Multi-step reaction with 6 steps 1.1: toluene-4-sulfonic acid / tetrahydrofuran / 3 h / 20 °C / Cooling; Large scale 2.1: tetrahydrofuran; diethyl ether / 8 h / 0 - 20 °C / Cooling; Large scale 3.1: trimethyl orthoformate; toluene-4-sulfonic acid / dichloromethane / 5 h / 20 - 25 °C / Large scale 4.1: Hexafluoroacetone; dihydrogen peroxide / dichloromethane; pyridine / -5 - 5 °C / Large scale 5.1: magnesium; copper(l) chloride / tetrahydrofuran / 3 h / 25 - 50 °C / Large scale 5.2: 2 h / 10 - 20 °C / Large scale 6.1: hydrogenchloride / 2 h / 25 °C View Scheme
Multi-step reaction with 6 steps 1.1: toluene-4-sulfonic acid / tetrahydrofuran / 4 h / 20 °C / Cooling; Large scale 2.1: tetrahydrofuran; 2-methyltetrahydrofuran / 0 - 10 °C 3.1: trimethyl orthoformate; toluene-4-sulfonic acid / dichloromethane / 5 h / 20 - 25 °C / Large scale 4.1: Hexafluoroacetone; dihydrogen peroxide / dichloromethane; pyridine / -5 - 5 °C / Large scale 5.1: magnesium; copper(l) chloride / tetrahydrofuran / 3 h / 25 - 50 °C / Large scale 5.2: 2 h / 10 - 20 °C / Large scale 6.1: hydrogenchloride / 2 h / 25 °C View Scheme
Multi-step reaction with 6 steps 1.1: toluene-4-sulfonic acid / tetrahydrofuran / 4 h / 20 °C / Cooling; Large scale 2.1: tetrahydrofuran; 2-methyltetrahydrofuran / 0 - 10 °C 3.1: trimethyl orthoformate; toluene-4-sulfonic acid / dichloromethane / 5 h / 20 - 25 °C / Large scale 4.1: Hexafluoroacetone; dihydrogen peroxide / dichloromethane; pyridine / -5 - 5 °C / Large scale 5.1: magnesium; copper(l) chloride / tetrahydrofuran / 3 h / 25 - 50 °C / Large scale 5.2: 2 h / 10 - 20 °C / Large scale 6.1: hydrogenchloride / 2 h / 25 °C View Scheme
Multi-step reaction with 6 steps 1.1: toluene-4-sulfonic acid / tetrahydrofuran / 4 h / 20 °C / Cooling; Large scale 2.1: tetrahydrofuran; 2-methyltetrahydrofuran / 0 - 10 °C 3.1: trimethyl orthoformate; toluene-4-sulfonic acid / dichloromethane / 5 h / 20 - 25 °C / Large scale 4.1: Hexafluoroacetone; dihydrogen peroxide / dichloromethane; pyridine / -5 - 5 °C / Large scale 5.1: magnesium; copper(l) chloride / tetrahydrofuran / 3 h / 25 - 50 °C / Large scale 5.2: 2 h / 10 - 20 °C / Large scale 6.1: hydrogenchloride / 2 h / 25 °C View Scheme

3,3-ethylenedioxy-17β-cyano-17α-chloromethyl(dimethyl)siloxy estren-5(10),9(11)diene (290825-36-4) → CDB-3236 (159811-51-5)

Conditions	Yield
Multi-step reaction with 4 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 4.1: 88 percent / aq. H2SO4 / ethanol / 1 h / Heating View Scheme

3-(ethylenedioxy)estra-5α,10α-epoxy-17α-ethynyl-17β-hydroxy-9(11)-ene (137532-55-9) → CDB-3236 (159811-51-5)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: magnesium; iodine / tetrahydrofuran / 20 - 50 °C / Inert atmosphere 1.2: 1 h / 0 °C / Inert atmosphere 2.1: triethylamine; acetic acid / Inert atmosphere 3.1: sodium methylate / methanol 4.1: Acidic conditions View Scheme
Multi-step reaction with 5 steps 1.1: magnesium; iodine / tetrahydrofuran / 20 - 50 °C / Inert atmosphere 1.2: 1 h / 0 °C / Inert atmosphere 2.1: sulfuric acid / water; ethanol / 2 h / 70 °C / Inert atmosphere 3.1: triethylamine / tetrahydrofuran / 2 h / -78 - -70 °C / Inert atmosphere 4.1: sodium methylate / methanol / 1 h / 70 °C / Inert atmosphere 4.2: 2 h / 70 °C / Inert atmosphere 5.1: hydrogenchloride / methanol / 0.5 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: magnesium / tetrahydrofuran; ethylene dibromide / 3 h / 45 °C / Industrial scale 1.2: 0 °C / Industrial scale 2.1: triethylamine / dichloromethane / 0.08 h / 0 °C / Industrial scale 2.2: 2 h / -5 - 0 °C / Industrial scale 3.1: methanol / 2.5 h / 70 °C / Industrial scale 3.2: 5 h / 70 °C / Industrial scale 4.1: hydrogenchloride / methanol; water / 1 h / 20 °C / Industrial scale View Scheme

4-bromo-N,N-dimethylaniline (586-77-6) → CDB-3236 (159811-51-5)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: magnesium; iodine / tetrahydrofuran / 20 - 50 °C / Inert atmosphere 1.2: 1 h / 0 °C / Inert atmosphere 2.1: triethylamine; acetic acid / Inert atmosphere 3.1: sodium methylate / methanol 4.1: Acidic conditions View Scheme
Multi-step reaction with 5 steps 1.1: magnesium; iodine / tetrahydrofuran / 20 - 50 °C / Inert atmosphere 1.2: 1 h / 0 °C / Inert atmosphere 2.1: sulfuric acid / water; ethanol / 2 h / 70 °C / Inert atmosphere 3.1: triethylamine / tetrahydrofuran / 2 h / -78 - -70 °C / Inert atmosphere 4.1: sodium methylate / methanol / 1 h / 70 °C / Inert atmosphere 4.2: 2 h / 70 °C / Inert atmosphere 5.1: hydrogenchloride / methanol / 0.5 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: magnesium / tetrahydrofuran; dichloromethane / 3 h / 40 - 50 °C / Large scale 1.2: 2 h / 10 - 20 °C / Cooling with ice; Large scale 2.1: hydrogenchloride; water / 2 h / 25 °C View Scheme

3,3-ethylenedioxy-5α,17β-dihydroxy-11β-[4-(N,N-dimethylamino)phenyl]-19-nor-17α-pregn-9-ene-21-ethyne (91934-95-1) → CDB-3236 (159811-51-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine; acetic acid / Inert atmosphere 2: sodium methylate / methanol 3: Acidic conditions View Scheme
Multi-step reaction with 4 steps 1.1: sulfuric acid / water; ethanol / 2 h / 70 °C / Inert atmosphere 2.1: triethylamine / tetrahydrofuran / 2 h / -78 - -70 °C / Inert atmosphere 3.1: sodium methylate / methanol / 1 h / 70 °C / Inert atmosphere 3.2: 2 h / 70 °C / Inert atmosphere 4.1: hydrogenchloride / methanol / 0.5 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: hydrogenchloride / water / 25 °C 1.2: 25 °C 2.1: triethylamine / dichloromethane / -60 °C 3.1: methanol / 6 h / 64 - 65 °C 4.1: acetic acid / water / 1 h / 25 °C View Scheme
Multi-step reaction with 4 steps 1.1: hydrogenchloride / water / 25 °C 1.2: 25 °C 2.1: triethylamine / dichloromethane / 0.5 h / 25 - 30 °C 3.1: methanol / 6 h / 64 - 65 °C 4.1: acetic acid / water / 1 h / 25 °C View Scheme
Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / 0.08 h / 0 °C / Industrial scale 1.2: 2 h / -5 - 0 °C / Industrial scale 2.1: methanol / 2.5 h / 70 °C / Industrial scale 2.2: 5 h / 70 °C / Industrial scale 3.1: hydrogenchloride / methanol; water / 1 h / 20 °C / Industrial scale View Scheme

3-(ethylenedioxy)estra-5,10-epoxy-17α-ethynyl-17β-hydroxy-9(11)-ene → CDB-3236 (159811-51-5)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: magnesium; iodine / tetrahydrofuran / 20 - 50 °C / Inert atmosphere 1.2: 1 h / 0 °C / Inert atmosphere 2.1: triethylamine; acetic acid / Inert atmosphere 3.1: sodium methylate / methanol 4.1: Acidic conditions View Scheme
Multi-step reaction with 5 steps 1.1: magnesium; iodine / tetrahydrofuran / 20 - 50 °C / Inert atmosphere 1.2: 1 h / 0 °C / Inert atmosphere 2.1: sulfuric acid / water; ethanol / 2 h / 70 °C / Inert atmosphere 3.1: triethylamine / tetrahydrofuran / 2 h / -78 - -70 °C / Inert atmosphere 4.1: sodium methylate / methanol / 1 h / 70 °C / Inert atmosphere 4.2: 2 h / 70 °C / Inert atmosphere 5.1: hydrogenchloride / methanol / 0.5 h / 20 °C View Scheme

17α-ethynyl-17β-hydroxy-11β-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3-one → CDB-3236 (159811-51-5)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: triethylamine / tetrahydrofuran / 2 h / -78 - -70 °C / Inert atmosphere 2.1: sodium methylate / methanol / 1 h / 70 °C / Inert atmosphere 2.2: 2 h / 70 °C / Inert atmosphere 3.1: hydrogenchloride / methanol / 0.5 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / -60 °C 2: methanol / 6 h / 64 - 65 °C 3: acetic acid / water / 1 h / 25 °C View Scheme
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 0.5 h / 25 - 30 °C 2: methanol / 6 h / 64 - 65 °C 3: acetic acid / water / 1 h / 25 °C View Scheme

11β-(4-N,N-dimethylaminophenyl)-21-(phenyl-sulfinyl)-19-norpregna-4,9,17(20),20-tetraene-3-one → CDB-3236 (159811-51-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium methylate / methanol / 1 h / 70 °C / Inert atmosphere 1.2: 2 h / 70 °C / Inert atmosphere 2.1: hydrogenchloride / methanol / 0.5 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: methanol / 6 h / 64 - 65 °C 2: acetic acid / water / 1 h / 25 °C View Scheme

3-(ethylenedioxy)estra-5,10-epoxy-9(11)-ene-17-one (786698-67-7) → CDB-3236 (159811-51-5)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: tetrahydrofuran / 1 h / 0 °C / Inert atmosphere 2.1: magnesium; iodine / tetrahydrofuran / 20 - 50 °C / Inert atmosphere 2.2: 1 h / 0 °C / Inert atmosphere 3.1: triethylamine; acetic acid / Inert atmosphere 4.1: sodium methylate / methanol 5.1: Acidic conditions View Scheme
Multi-step reaction with 6 steps 1.1: tetrahydrofuran / 1 h / 0 °C / Inert atmosphere 2.1: magnesium; iodine / tetrahydrofuran / 20 - 50 °C / Inert atmosphere 2.2: 1 h / 0 °C / Inert atmosphere 3.1: sulfuric acid / water; ethanol / 2 h / 70 °C / Inert atmosphere 4.1: triethylamine / tetrahydrofuran / 2 h / -78 - -70 °C / Inert atmosphere 5.1: sodium methylate / methanol / 1 h / 70 °C / Inert atmosphere 5.2: 2 h / 70 °C / Inert atmosphere 6.1: hydrogenchloride / methanol / 0.5 h / 20 °C View Scheme

(8S,13S,14S,17R)-17-ethynyl-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2’-[1,3]dioxolan]-17-ol (5490-76-6) → CDB-3236 (159811-51-5)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: Hexafluoroacetone; dihydrogen peroxide; sodium phosphate dibasic dodecahydrate / water; dichloromethane / Inert atmosphere 2.1: magnesium; iodine / tetrahydrofuran / 20 - 50 °C / Inert atmosphere 2.2: 1 h / 0 °C / Inert atmosphere 3.1: triethylamine; acetic acid / Inert atmosphere 4.1: sodium methylate / methanol 5.1: Acidic conditions View Scheme
Multi-step reaction with 6 steps 1.1: Hexafluoroacetone; dihydrogen peroxide; sodium phosphate dibasic dodecahydrate / water; dichloromethane / Inert atmosphere 2.1: magnesium; iodine / tetrahydrofuran / 20 - 50 °C / Inert atmosphere 2.2: 1 h / 0 °C / Inert atmosphere 3.1: sulfuric acid / water; ethanol / 2 h / 70 °C / Inert atmosphere 4.1: triethylamine / tetrahydrofuran / 2 h / -78 - -70 °C / Inert atmosphere 5.1: sodium methylate / methanol / 1 h / 70 °C / Inert atmosphere 5.2: 2 h / 70 °C / Inert atmosphere 6.1: hydrogenchloride / methanol / 0.5 h / 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: disodium hydrogenphosphate; dihydrogen peroxide / dichloromethane / 18 h / 20 °C / Industrial scale 2.1: magnesium / tetrahydrofuran; ethylene dibromide / 3 h / 45 °C / Industrial scale 2.2: 0 °C / Industrial scale 3.1: triethylamine / dichloromethane / 0.08 h / 0 °C / Industrial scale 3.2: 2 h / -5 - 0 °C / Industrial scale 4.1: methanol / 2.5 h / 70 °C / Industrial scale 4.2: 5 h / 70 °C / Industrial scale 5.1: hydrogenchloride / methanol; water / 1 h / 20 °C / Industrial scale View Scheme

C36H43NO4S → CDB-3236 (159811-51-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium methylate / methanol 2: Acidic conditions View Scheme

C31H43NO5 → CDB-3236 (159811-51-5)

Conditions	Yield
Acidic conditions;

ethylene deltenone (5571-36-8) → CDB-3236 (159811-51-5)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: tetrahydrofuran / 0 °C 2.1: Hexafluoroacetone; dihydrogen peroxide; sodium phosphate dibasic dodecahydrate / water; dichloromethane / Inert atmosphere 3.1: magnesium; iodine / tetrahydrofuran / 20 - 50 °C / Inert atmosphere 3.2: 1 h / 0 °C / Inert atmosphere 4.1: triethylamine; acetic acid / Inert atmosphere 5.1: sodium methylate / methanol 6.1: Acidic conditions View Scheme
Multi-step reaction with 7 steps 1.1: tetrahydrofuran / 0 °C 2.1: Hexafluoroacetone; dihydrogen peroxide; sodium phosphate dibasic dodecahydrate / water; dichloromethane / Inert atmosphere 3.1: magnesium; iodine / tetrahydrofuran / 20 - 50 °C / Inert atmosphere 3.2: 1 h / 0 °C / Inert atmosphere 4.1: sulfuric acid / water; ethanol / 2 h / 70 °C / Inert atmosphere 5.1: triethylamine / tetrahydrofuran / 2 h / -78 - -70 °C / Inert atmosphere 6.1: sodium methylate / methanol / 1 h / 70 °C / Inert atmosphere 6.2: 2 h / 70 °C / Inert atmosphere 7.1: hydrogenchloride / methanol / 0.5 h / 20 °C View Scheme
Multi-step reaction with 7 steps 1.1: acetic acid / methanol / 20 °C 2.1: toluene-4-sulfonic acid / tetrahydrofuran / 3 h / 20 °C / Cooling; Large scale 3.1: tetrahydrofuran; diethyl ether / 8 h / 0 - 20 °C / Cooling; Large scale 4.1: trimethyl orthoformate; toluene-4-sulfonic acid / dichloromethane / 5 h / 20 - 25 °C / Large scale 5.1: Hexafluoroacetone; dihydrogen peroxide / dichloromethane; pyridine / -5 - 5 °C / Large scale 6.1: magnesium; copper(l) chloride / tetrahydrofuran / 3 h / 25 - 50 °C / Large scale 6.2: 2 h / 10 - 20 °C / Large scale 7.1: hydrogenchloride / 2 h / 25 °C View Scheme

3,3,20,20-bis(ethylene-dioxy)-17α-hydroxy-5β,10β-epoxy-19-norpregna-9(11)-ene → CDB-3236 (159811-51-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: magnesium / tetrahydrofuran; dichloromethane / 3 h / 40 - 50 °C / Large scale 1.2: 2 h / 10 - 20 °C / Cooling with ice; Large scale 2.1: hydrogenchloride; water / 2 h / 25 °C View Scheme

17α-[(±)1-(1-n-propyloxyl)ethyl]oxyl-17β-cyano-3,3-(ethylene-dioxy)-19-norpregna-5(10),9(11)-diene → CDB-3236 (159811-51-5)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: tetrahydrofuran; 2-methyltetrahydrofuran / 0 - 10 °C 2.1: trimethyl orthoformate; toluene-4-sulfonic acid / dichloromethane / 5 h / 20 - 25 °C / Large scale 3.1: Hexafluoroacetone; dihydrogen peroxide / dichloromethane; pyridine / -5 - 5 °C / Large scale 4.1: magnesium; copper(l) chloride / tetrahydrofuran / 3 h / 25 - 50 °C / Large scale 4.2: 2 h / 10 - 20 °C / Large scale 5.1: hydrogenchloride / 2 h / 25 °C View Scheme

17α-[(±)1-(1-isobutyloxyl)ethyl]oxyl-17β-cyano-3,3-(ethylene-dioxy)-19-norpregna-5(10),9(11)-diene → CDB-3236 (159811-51-5)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: tetrahydrofuran; 2-methyltetrahydrofuran / 0 - 10 °C 2.1: trimethyl orthoformate; toluene-4-sulfonic acid / dichloromethane / 5 h / 20 - 25 °C / Large scale 3.1: Hexafluoroacetone; dihydrogen peroxide / dichloromethane; pyridine / -5 - 5 °C / Large scale 4.1: magnesium; copper(l) chloride / tetrahydrofuran / 3 h / 25 - 50 °C / Large scale 4.2: 2 h / 10 - 20 °C / Large scale 5.1: hydrogenchloride / 2 h / 25 °C View Scheme

17α-[(±)1-(1-tetrahydropyran)ethyl]oxyl-17β-cyano-3,3-(ethylene-dioxy)-19-norpregna-5(10),9(11)-diene → CDB-3236 (159811-51-5)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: tetrahydrofuran; 2-methyltetrahydrofuran / 0 - 10 °C 2.1: trimethyl orthoformate; toluene-4-sulfonic acid / dichloromethane / 5 h / 20 - 25 °C / Large scale 3.1: Hexafluoroacetone; dihydrogen peroxide / dichloromethane; pyridine / -5 - 5 °C / Large scale 4.1: magnesium; copper(l) chloride / tetrahydrofuran / 3 h / 25 - 50 °C / Large scale 4.2: 2 h / 10 - 20 °C / Large scale 5.1: hydrogenchloride / 2 h / 25 °C View Scheme

17α-hydroxy-19-norpregna-5(10),9(11)-diene-3,20-dione → CDB-3236 (159811-51-5)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: trimethyl orthoformate; toluene-4-sulfonic acid / dichloromethane / 5 h / 20 - 25 °C / Large scale 2.1: Hexafluoroacetone; dihydrogen peroxide / dichloromethane; pyridine / -5 - 5 °C / Large scale 3.1: magnesium; copper(l) chloride / tetrahydrofuran / 3 h / 25 - 50 °C / Large scale 3.2: 2 h / 10 - 20 °C / Large scale 4.1: hydrogenchloride / 2 h / 25 °C View Scheme

3,3,20,20-bis(ethylenedioxy)-5α,17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl]-19-norgestrel-9(11)-ene → CDB-3236 (159811-51-5)

Conditions	Yield
With hydrogenchloride at 25℃; for 2h;

C25H35NO4 → CDB-3236 (159811-51-5)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: tetrahydrofuran; diethyl ether / 8 h / 0 - 20 °C / Cooling; Large scale 2.1: trimethyl orthoformate; toluene-4-sulfonic acid / dichloromethane / 5 h / 20 - 25 °C / Large scale 3.1: Hexafluoroacetone; dihydrogen peroxide / dichloromethane; pyridine / -5 - 5 °C / Large scale 4.1: magnesium; copper(l) chloride / tetrahydrofuran / 3 h / 25 - 50 °C / Large scale 4.2: 2 h / 10 - 20 °C / Large scale 5.1: hydrogenchloride / 2 h / 25 °C View Scheme

17α-[(±)1-(1-ethoxyl)ethyl]oxyl-17β-cyano-3,3-(ethylene-dioxy)-19-norpregna-5(10),9(11)-diene → CDB-3236 (159811-51-5)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: tetrahydrofuran; 2-methyltetrahydrofuran / 0 - 10 °C 2.1: trimethyl orthoformate; toluene-4-sulfonic acid / dichloromethane / 5 h / 20 - 25 °C / Large scale 3.1: Hexafluoroacetone; dihydrogen peroxide / dichloromethane; pyridine / -5 - 5 °C / Large scale 4.1: magnesium; copper(l) chloride / tetrahydrofuran / 3 h / 25 - 50 °C / Large scale 4.2: 2 h / 10 - 20 °C / Large scale 5.1: hydrogenchloride / 2 h / 25 °C View Scheme

11β-(4-N,N-dimethylaminophenyl)-21-(phenyl-sulfinyl)-19-norpregna-4,9,17(20),20-tetraene-3-one → 11β-(4-(N,N-dimethylamino)phenyl)-17β-hydroxy-19-norpregna-4,9-diene-3,20-dione + CDB-3236 (159811-51-5)

Conditions	Yield
Stage #1: 11β-(4-N,N-dimethylaminophenyl)-21-(phenyl-sulfinyl)-19-norpregna-4,9,17(20),20-tetraene-3-one With sodium methylate; phosphorous acid trimethyl ester Stage #2: With hydrogenchloride

C24H34O6 → CDB-3236 (159811-51-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: magnesium; copper dichloride / tetrahydrofuran; ethylene dibromide / 2.5 h / 10 - 25 °C 2: hydrogenchloride / water / 2 h / 25 °C View Scheme

acetic anhydride (108-24-7) + CDB-3236 (159811-51-5) → ulipristal acetate (126784-99-4)

Conditions	Yield
Stage #1: acetic anhydride With perchloric acid at -10℃; Inert atmosphere; Stage #2: CDB-3236 In dichloromethane at -30 - -20℃; for 2h; Inert atmosphere;	93.4%
Stage #1: acetic anhydride; CDB-3236 With perchloric acid In dichloromethane at -10℃; for 3h; Industrial scale; Stage #2: With pyrographite In isopropyl alcohol for 0.5h; Industrial scale;	90.9%
With perchloric acid In dichloromethane at -25 - -20℃; for 0.833333h;	85%

trifluoroacetic anhydride (96-63-9) + CDB-3236 (159811-51-5) → ulipristal acetate (126784-99-4)

Conditions	Yield
With toluene-4-sulfonic acid In dichloromethane at 0℃; for 0.333333h;	68%

CDB-3236 (159811-51-5) → 11β-(4-N-methylaminophenyl)-17α-hydroxy-19-norpregna-4,9-diene-3,20-dione (159681-67-1)

Conditions	Yield
With iodine; calcium oxide In tetrahydrofuran; methanol

Upstream product

• 137532-55-9 3-(ethylenedioxy)estra-5α,10α-epoxy-17α-ethynyl-17β-hydroxy-9(11)-ene 
• 586-77-6 4-bromo-N,N-dimethylaniline 
• 91934-95-1 3,3-ethylenedioxy-5α,17β-dihydroxy-11β-[4-(N,N-dimethylamino)phenyl]-19-nor-17α-pregn-9-ene-21-ethyne 
• 786698-67-7 3-(ethylenedioxy)estra-5,10-epoxy-9⁽¹¹⁾-ene-17-one 
• 5490-76-6 (8S,13S,14S,17R)-17-ethynyl-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2’-[1,3]dioxolan]-17-ol 
• 5571-36-8 ethylene deltenone 

Downstream Products

• 126784-99-4 ulipristal acetate 
• 159681-67-1 11β-(4-N-methylaminophenyl)-17α-hydroxy-19-norpregna-4,9-diene-3,20-dione 

Relevant academic research and scientific papers

Acetic acid wu lisi he and its intermediate preparation method

The invention discloses a preparation method of ulipristal acetate and an intermediate thereof, and belongs to the field of pharmaceutical synthesis. The preparation method of the ulipristal acetate comprises the following steps: by taking 3,3-(ethylenedioxy)-19-methylestra-5(10),9(11)-diene-3,17-diketone as raw material, enabling the raw material to react with sodium acetylide or potassium acetylide to obtain a compound III, carrying out high-selectivity epoxidation by oxide to obtain a compound IV, subsequently enabling the compound IV to react with 4-(N,N-dimethyl amino) phenyl magnesium bromide Grignard reagent to obtain a compound V, then enabling the compound V to react with phenyl sulfonic acid chloride to obtain a compound VI, enabling the compound VI to respectively react with sodium methoxide and trimethyl phosphate to obtain a compound VII, hydrolyzing and removing a protection group to obtain a compound VIII, finally carrying out acetylation reaction to obtain the ulipristal acetate, wherein the reaction formulae are as shown in the description. The method is short in synthetic route, mild in reaction conditions, high in yield and purity of products, low in cost, stable and controllable in quality, and is suitable for industrial production.

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.

Ulipristal acetate impurities and preparation and detection method thereof

The invention provides ulipristal acetate impurity compounds and a preparation method thereof, and particularly provides a novel compound impurity F (a compound F) and a novel compound impurity K (a compound K). 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 ULIPRISTAL ACETATE AND ITS 4'-ACETYL ANALOGUE

The present invention relates to a new process for the synthesis of compounds of formula (I) (wherein the meaning of R is dimethylamino or acetyl group) using the compound of formula (II) (wherein the meaning of R is dimethylamino or 2-methyl-1,3-dioxolan-2-yl group) as starting material, as well as to the intermediate of the process.

First synthesis and characterization for the stereoisomers of Ulipristal acetate

The three stereoisomers, 11α,17α-isomer I, 11α,17β-isomer II and 11β,17β-isomer III are related substances of the selective progesterone receptor modulator Ulipristal acetate. Herein, we presented an efficient and practical synthesis approach to deliver t

Method for preparing ulipristal acetate and key intermediate thereof

A method as well as new intermediates for preparing Ulipristal acetate (a compound I) and a method for preparing the new intermediates are provided. The intermediate in a constitutional formula IV is conductive to reacting with methyl lithium or methyl Grignard reagent, a protective group is easy to be removed after a reaction, side reactions are few, a mid-term treatment is simple, the reagents used are cheap, costs are low and a yield is high, if a compound in a constitutional formula V is obtained by the reaction of a compound in a constitutional formula III and the intermediate in the constitutional formula IV, the yield of a two-step reaction is 75%, a purity is above 98%. wherein R is defined in the specification.

ULIPRISTAL ACETATE PREPARATION METHOD AND INTERMEDIATE THEREOF

A method as well as new intermediates for preparing Ulipristal acetate (a compound I) and a method for preparing the new intermediates are provided. The intermediate in a constitutional formula IV is conductive to reacting with methyl lithium or methyl Grignard reagent, a protective group is easy to be removed after a reaction, side reactions are few, a mid-term treatment is simple, the reagents used are cheap, costs are low and the yield is high, if a compound in a constitutional formula V is obtained by the reaction of a compound in a constitutional formula III and the intermediate in the constitutional formula IV, the yield of a two-step reaction is 75%, a purity is above 98%. wherein R is defined in the specification.

NOVEL PROCESS AND INTERMEDIATE FOR PREPARATION OF ULIPRISTAL

The present invention is related to a novel process for the preparation of ulipristal (I) that comprises reaction of 17-α-ethynyl-17-β-hydroxy-11-β-(4-N,N-dimethylamino phenyl)- 9-norpregna-4,9-diene-3-one (III) with phenyl sulphenyl chloride (IVa) or p-nitro phenyl sulphenyl chloride (IVb) in the presence of organic base and solvent to give sulfoxide (Va) or (Vb) respectively. Sulfoxides (Va) or (Vb) are reacted with alkali metal alkoxide in alcoholic solvent followed by treatment with aqueous acid. The present invention also relates to novel intermediate 11-β-(4-N,N-dimethylaminophenyl)-21(p- nitro-phenyl-sulphinyl)-19-norpregna-4(5), 9(10), 17(20) 20-tetraene, 3-one (Vb).

A simple and convenient synthetic route to Ulipristal acetate

We set out to describe a new and efficient route for preparing Ulipristal acetate with a good yield. The selected epoxidization conditions gave out 80% of 5α,10α-epoxide 2a in the two diastereoisomers which greatly improved the yield of 11β-substituted isomer 4a. And phenyl-sulfinyl compound 6 was synthesized from ketone 5 directly treated with phenylsulfenyl chloride in the presence of triethylamine. These synthetic procedures is only 8 steps, less than currently reported in the literature, but more suitable for industrial process.

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.