84371-57-3

Usage

Chemical Properties

Pale Yellow Solid

Uses

Intermediate in the preparation of Mifepristone derivatives.

Synthetic route

1-propynylmagnesium bromide (16466-97-0, 13254-27-8) + (5'R,10'R,13'S)-13'-methyl-1',2',6',7',8',12',13',14',15',16'-decahydro-17'H-spiro[1,3-dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-one (39931-88-9, 116003-08-8, 39931-87-8) → (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3)

Conditions	Yield
Stage #1: 1-propynylmagnesium bromide; (5'R,10'R,13'S)-13'-methyl-1',2',6',7',8',12',13',14',15',16'-decahydro-17'H-spiro[1,3-dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-one In tetrahydrofuran at 0℃; for 2h; Stage #2: With ammonium chloride In water	100%

(8S,13S,14S,17S)-13-methyl-17-(prop-1-yn-1-yl)-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2'-[1,3]dioxolan]-17-ol (84371-69-7) → (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane	35%
With disodium hydrogenphosphate; dihydrogen peroxide; Hexafluoroacetone In dichloromethane; water at 0 - 20℃; for 2.16667h;	1.8 g

(5'R,10'R,13'S,16'R)-13',16'-dimethyl-1',2',6',7',8',12',13',14',15'-nonahydro-17'H-spiro[1,3-dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-one (639520-94-8) + 1-propynylmagnesium bromide (16466-97-0, 13254-27-8) → (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3)

Conditions	Yield
Stage #1: (5'R,10'R,13'S,16'R)-13',16'-dimethyl-1',2',6',7',8',12',13',14',15'-nonahydro-17'H-spiro[1,3-dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-one; 1-propynylmagnesium bromide In tetrahydrofuran at 0℃; for 2.5h; Stage #2: With ammonium chloride In tetrahydrofuran; water	29%

1-propynyl lithium (4529-04-8) + (5'R,10'R,13'S)-13'-methyl-1',2',6',7',8',12',13',14',15',16'-decahydro-17'H-spiro[1,3-dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-one (39931-88-9, 116003-08-8, 39931-87-8) → (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3)

Conditions	Yield
In tetrahydrofuran; hexane for 1h; Yield given;

ethylene deltenone (5571-36-8) → (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / tetrahydrofuran 2: 35 percent / m-CPBA / CH2Cl2 View Scheme
Multi-step reaction with 2 steps 1: 76.1 percent / 30percent H2O2, hexachloroacetone / CH2Cl2 / 72 h 2: tetrahydrofuran; hexane / 1 h View Scheme
Multi-step reaction with 2 steps 1: tetrahydrofuran / 0 - 20 °C 2: Hexafluoroacetone; disodium hydrogenphosphate; dihydrogen peroxide / dichloromethane; water / 2.17 h / 0 - 20 °C View Scheme
Multi-step reaction with 2 steps 1: tetrahydrofuran / 0 - 25 °C / Inert atmosphere 2: Hexafluoroacetone; dihydrogen peroxide / 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; aq. phosphate buffer / 2.17 h / 0 - 20 °C / Inert atmosphere View Scheme

(8S,13S,14S,17S)-13-methyl-17-(prop-1-yn-1-yl)-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2'-[1,3]dioxolan]-17-ol (84371-69-7) → 5β,10β-epoxy-3,3-ethylenedioxy-17β-hydroxy-17α-(1-propynyl)estra-9(11)-ene + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3)

Conditions	Yield
With pyridine; 1,1,1,3,3,3-hexachloro-propan-2-one; Br(1-)*C26H29N2O(1+); dihydrogen peroxide In dichloromethane; water at 20℃; for 48h; optical yield given as %de; diastereoselective reaction;
With dihydrogen peroxide; Hexafluoroacetone In aq. phosphate buffer; 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran at 0 - 20℃; for 2.16667h; Inert atmosphere;	A n/a B n/a

4-(N-isopropyl-N-methylamino)phenyl bromide (61684-98-8) + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → 5α-17β-dihydroxy-11β-[4-(N-isopropyl-N-methylamino)phenyl]-17α-ethynyl-3,3-(ethane-1,2-diyldioxy)-estra-9-ene (883565-88-6)

Conditions	Yield
Stage #1: 4-(N-isopropyl-N-methylamino)phenyl bromide With magnesium In tetrahydrofuran for 0.416667h; Heating; Stage #2: (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol With copper(l) chloride In tetrahydrofuran at 6 - 7℃; for 0.5h;	100%

(5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) + 4-(N-tert-butyloxycarbonyl-N-methylamino)phenyl bromide (639520-70-0) → tert-butyl 4-((5R,11R,13S,17S)-5,17-dihydroxy-13-methyl-17-prop-1-ynyl-1,2,4,5,6,7,8,11,12,13,14,15,16,17-tetradecahydrospiro[cyclopenta[a]phenanthrene-3,2'-[1,3]dioxolan]-11-yl)phenyl(methyl)carbamate (639520-75-5)

Conditions

Yield

Stage #1: 4-(N-tert-butyloxycarbonyl-N-methylamino)phenyl bromide With iodine; magnesium In tetrahydrofuran at 20℃; for 0.416667h; Heating / reflux; Stage #2: With copper(l) iodide In tetrahydrofuran at 0℃; for 0.0333333h; Stage #3: (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol With ammonium chloride more than 3 stages;

90%

4-(N-isopropyl-N-trimethylsilylamino)phenyl bromide (883565-85-3) + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → 5α-17β-dihydroxy-11β-[4-(N-isopropyl-N-trimethylsilylamino)phenyl]-17α-ethynyl-3,3-(ethane-1,2-diyldioxy)-estra-9-ene (883565-86-4)

Conditions	Yield
Stage #1: 4-(N-isopropyl-N-trimethylsilylamino)phenyl bromide With magnesium In tetrahydrofuran for 0.416667h; Heating; Stage #2: (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol With copper(l) chloride In tetrahydrofuran at 6 - 7℃; for 0.5h;	75%

(4-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)magnesium bromide (36637-44-2) + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → C34H44O6 (934415-53-9)

Conditions	Yield
With copper(l) chloride In tetrahydrofuran	53%

(5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) + p-N-trimethylsilyl-N-methylaminophenylmagnesium bromide → 11β-(4-methylaminophenyl)-<3,3-(1,2-ethylenedioxybisoxy)>-17α-(1-propynyl)-estra-9-en-5α,7β-diol (104004-98-0)

Conditions	Yield
With ammonium chloride; copper(l) chloride 1.) THF, 6 h, 2.) THF; Yield given. Multistep reaction;

4-(N-methyl-N-cyclohexylamino)phenyl magnesium bromide (329971-57-5) + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → 3,3-ethylenedioxy-5α,17β-dihydroxy-11β-[4-(N-methyl-N-cyclohexylamino)phenyl]-17α-(1-propynyl)-9(10)-estrene (329971-39-3)

Conditions	Yield
With copper dichloride In tetrahydrofuran at 5℃; for 5h;

(5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → 17β-hydroxy-11β-[4-hydroxyphenyl]-17α-(1-propinyl)-estra-4,9-dien-3-one (88257-21-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 53 percent / CuCl / tetrahydrofuran 2: 75 percent / p-TSA View Scheme

(5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → 11-[4-(dimethyl-phosphinoyl)-phenyl]-17-hydroxy-13-methyl-17-prop-1-ynyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta[a]phenanthren-3-one

Conditions	Yield
Multi-step reaction with 4 steps 1: 53 percent / CuCl / tetrahydrofuran 2: 75 percent / p-TSA 3: 60 percent / NaH 4: Pd(OAc)2; dppb; i-Pr2NEt / microwave irradiation View Scheme

(5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → trifluoro-methanesulfonic acid 4-(17-hydroxy-13-methyl-3-oxo-17-prop-1-ynyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl ester (167846-17-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 53 percent / CuCl / tetrahydrofuran 2: 75 percent / p-TSA 3: 60 percent / NaH View Scheme

(5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → [4-(17-hydroxy-13-methyl-3-oxo-17-prop-1-ynyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-phosphonic acid diethyl ester

Conditions	Yield
Multi-step reaction with 4 steps 1: 53 percent / CuCl / tetrahydrofuran 2: 75 percent / p-TSA 3: 60 percent / NaH 4: Pd(OAc)2; dppb; i-Pr2NEt / microwave irradiation View Scheme

(5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → 11-[4-(diphenyl-phosphinoyl)-phenyl]-17-hydroxy-13-methyl-17-prop-1-ynyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta[a]phenanthren-3-one

Conditions	Yield
Multi-step reaction with 4 steps 1: 53 percent / CuCl / tetrahydrofuran 2: 75 percent / p-TSA 3: 60 percent / NaH 4: Pd(OAc)2; dppb; i-Pr2NEt / microwave irradiation View Scheme

1-bromo-2,6-difluoro4-methoxybenzene + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → C30H34F2O4

Conditions	Yield
Stage #1: 1-bromo-2,6-difluoro4-methoxybenzene With iodine; magnesium In tetrahydrofuran for 0.25h; Heating; Stage #2: (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol With copper(l) iodide In tetrahydrofuran at 0℃; Further stages.;

1-bromo-2,5-difluoro-4-methoxybenzene + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → C30H34F2O4

Conditions	Yield
Stage #1: 1-bromo-2,5-difluoro-4-methoxybenzene With iodine; magnesium In tetrahydrofuran for 0.25h; Heating; Stage #2: (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol With copper(l) iodide In tetrahydrofuran at 0℃; Further stages.;

C10H10BrClO (918823-90-2) + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → C33H39ClO4

Conditions	Yield
Stage #1: C10H10BrClO With iodine; magnesium In tetrahydrofuran for 0.25h; Heating; Stage #2: (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol With copper(l) iodide In tetrahydrofuran at 0℃; Further stages.;

2-bromo-1-fluoro-3,5-dimethoxybenzene (206860-47-1) + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → C31H37FO5

Conditions	Yield
Stage #1: 2-bromo-1-fluoro-3,5-dimethoxybenzene With iodine; magnesium In tetrahydrofuran for 0.25h; Heating; Stage #2: (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol With copper(l) iodide In tetrahydrofuran at 0℃; Further stages.;

1-bromo-4-methoxy-benzene (104-92-7) + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → C30H36O4

Conditions	Yield
Stage #1: 1-bromo-4-methoxy-benzene With iodine; magnesium In tetrahydrofuran for 0.25h; Heating; Stage #2: (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol With copper(l) iodide In tetrahydrofuran at 0℃; Further stages.;

4-Bromodiphenyl ether (101-55-3) + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → C35H38O4

Conditions	Yield
Stage #1: 4-Bromodiphenyl ether With iodine; magnesium In tetrahydrofuran for 0.25h; Heating; Stage #2: (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol With copper(l) iodide In tetrahydrofuran at 0℃; Further stages.;

(4-bromophenyl)thioanisole (104-95-0) + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → C30H36O3S

Conditions	Yield
Stage #1: (4-bromophenyl)thioanisole With iodine; magnesium In tetrahydrofuran for 0.25h; Heating; Stage #2: (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol With copper(l) iodide In tetrahydrofuran at 0℃; Further stages.;

4-bromo-3-methylanisole (27060-75-9) + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → C31H38O4

Conditions	Yield
Stage #1: 4-bromo-3-methylanisole With iodine; magnesium In tetrahydrofuran for 0.25h; Heating; Stage #2: (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol With copper(l) iodide In tetrahydrofuran at 0℃; Further stages.;

5-bromo-2-methoxy-1,3-dimethylbenzene (14804-38-7) + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → C32H40O4

Conditions	Yield
Stage #1: 5-bromo-2-methoxy-1,3-dimethylbenzene With iodine; magnesium In tetrahydrofuran for 0.25h; Heating; Stage #2: (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol With copper(l) iodide In tetrahydrofuran at 0℃; Further stages.;

4-bromo-4'-methoxylbiphenyl (58743-83-2) + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → C36H40O4

Conditions	Yield
Stage #1: 4-bromo-4'-methoxylbiphenyl With iodine; magnesium In tetrahydrofuran for 0.25h; Heating; Stage #2: (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol With copper(l) iodide In tetrahydrofuran at 0℃; Further stages.;

2-bromo-1,3,5-trimethoxybenzene (1131-40-4) + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → C32H40O6

Conditions	Yield
Stage #1: 2-bromo-1,3,5-trimethoxybenzene With iodine; magnesium In tetrahydrofuran for 0.25h; Heating; Stage #2: (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol With copper(l) iodide In tetrahydrofuran at 0℃; Further stages.;

4-Bromo-2-methylphenol (2362-12-1) + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → C30H36O4

Conditions	Yield
Stage #1: 4-Bromo-2-methylphenol With iodine; magnesium In tetrahydrofuran for 0.25h; Heating; Stage #2: (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol With copper(l) iodide In tetrahydrofuran at 0℃; Further stages.;

2-methyl-4-bromoanisole (14804-31-0) + (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol (84371-57-3) → C31H38O4

Conditions	Yield
Stage #1: 2-methyl-4-bromoanisole With iodine; magnesium In tetrahydrofuran for 0.25h; Heating; Stage #2: (5'R,8'S,10'R,13'S,14'S,17'S)-13'-methyl-17'-(prop-1-yn-1-yl)-1',2',7',8',12',13',14',15',16',17'-decahydro-4'H,6'H-spiro[[1,3]dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-ol With copper(l) iodide In tetrahydrofuran at 0℃; Further stages.;

Upstream product

• 84371-69-7 (8S,13S,14S,17S)-13-methyl-17-(prop-1-yn-1-yl)-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2'-[1,3]dioxolan]-17-ol 
• 639520-94-8 (5'R,10'R,13'S,16'R)-13',16'-dimethyl-1',2',6',7',8',12',13',14',15'-nonahydro-17'H-spiro[1,3-dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-one 
• 16466-97-0 1-propynylmagnesium bromide 
• 39931-88-9 (5'R,10'R,13'S)-13'-methyl-1',2',6',7',8',12',13',14',15',16'-decahydro-17'H-spiro[1,3-dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-one 
• 5571-36-8 ethylene deltenone 
• 4529-04-8 1-propynyl lithium 

Downstream Products

• 934415-53-9 C₃₄H₄₄O₆ 
• 329971-39-3 3,3-ethylenedioxy-5α,17β-dihydroxy-11β-[4-(N-methyl-N-cyclohexylamino)phenyl]-17α-(1-propynyl)-9(10)-estrene 

Relevant academic research and scientific papers

Discovery of a Potent and Selective Steroidal Glucocorticoid Receptor Antagonist (ORIC-101)

The glucocorticoid receptor (GR) has been linked to therapy resistance across a wide range of cancer types. Preclinical data suggest that antagonists of this nuclear receptor may enhance the activity of anticancer therapy. The first-generation GR antagonist mifepristone is currently undergoing clinical evaluation in various oncology settings. Structure-based modification of mifepristone led to the discovery of ORIC-101 (28), a highly potent steroidal GR antagonist with reduced androgen receptor (AR) agonistic activity amenable for dosing in androgen receptor positive tumors and with improved CYP2C8 and CYP2C9 inhibition profile to minimize drug-drug interaction potential. Unlike mifepristone, 28 could be codosed with chemotherapeutic agents readily metabolized by CYP2C8 such as paclitaxel. Furthermore, 28 demonstrated in vivo antitumor activity by enhancing response to chemotherapy in the GR+ OVCAR5 ovarian cancer xenograft model. Clinical evaluation of safety and therapeutic potential of 28 is underway.

INHIBITORS OF GLUCOCORTICOID RECEPTOR

The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer and hypercortisolism.

Phase-Transfer catalysed enantioselective epoxidation of Estra-δ5(10),9(11)- diene using chiral ammonium salts derived from cinchona alkaloids

A modified phase-transfer catalysed enantioselective epoxidation of estra-δ5(10),9(11)-diene, an important intermediate of anti-early pregnancy drug mifepristone 1, have been determined and investigated. Eight chiral ammonium salts (PTC A-H), used as phase-transfer catalysts, have been synthesized from cinchona alkaloids. Among them, PTC G and PTC H have exhibited satisfying catalytic activity to improve the ratio of α/β. epoxide up to 7:1.

17-PHOSPHOROUS STEROID DERIVATIVES USEFUL AS PROGESTERONE RECEPTOR MODULATORS

The present invention is directed to novel 17-phosphorous steroid derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by a progesterone or glucocorticoid receptor.

11-PHOSPHOROUS STEROID DERIVATIVES USEFUL AS PROGESTERONE RECEPTOR MODULATORS

The present invention is directed to novel 11-phosphorous steroid derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by a progesterone or glucocorticoid receptor.

Discovery of novel phosphorus-containing steroids as selective glucocorticoid receptor antagonist

Mifepristone is a non-selective antagonist of 3-oxosteroid receptors with both abortifacient and anti-diabetic activities. For glucocorticoid receptor (GR) program, we sought an unexplored, synthetically accessible phosphorus-containing steroidal mimetic of mifepristone, suitable for parallel synthesis of analogues. One compound 4a, with high oral bioavailability (59%) in rat, exhibited functional antagonism of GR in oral glucose tolerance test (OGTT). Thus this series of compounds might be potentially useful for the treatment of type II diabetes.

GLUCOCORTICOID RECEPTOR LIGANDS FOR THE TREATMENT OF METABOLIC DISORDERS

This invention relates to novel compounds that are liver selective glucocorticoid receptor antagonists, to methods of preparing such compounds, and to methods for using such compounds in the regulation of metabolism, especially lowering serum glucose levels, insulin levels, or lipid levels, and/or decreasing body weight.

Synthesis and characterization of tritium-labelled RU486

[3H]RU38486 (RU486) was synthesized from its penultimate precursor, desmethyl RU486, by substitution of the secondary amine with tritiated methyl iodide; specific activity 85 Ci/mmol. Ligand binding studies confirm that RU486 binds with high affinity to human progesterone receptor type A (PR-A) and progesterone receptor type B (PR-B).