1625-39-4

Basic information

• Product Name: 11-beta,17-alpha,21-trihydroxy-6-alpha-methylpregn-4-ene-3,20-dione
• Synonyms: 11-beta,17-alpha,21-trihydroxy-6-alpha-methylpregn-4-ene-3,20-dione;11β,17,21-Trihydroxy-6α-methylpregn-4-ene-3,20-dione;6α-Methylhydrocortisone;(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-17-(2-hydroxyacetyl)-6,10,13-trimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one;(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-17-(2-hydroxyethanoyl)-6,10,13-trimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one;(6S,8S,9S,10R,11S,13S,14S,17R)-17-glycoloyl-11,17-dihydroxy-6,10,13-trimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one;Methylprednisolone EP Impurity F
• CAS NO: 1625-39-4
• Molecular Formula: C₂₂H₃₂O₅
• Molecular Weight: 376.48648
• EINECS: 216-614-9
• Product Categories: Pharmaceutical Raw Materials;Intermediates & Fine Chemicals;Pharmaceuticals;Steroids
• Mol File: 1625-39-4.mol
• Article Data: 5

Chemical Properties

• Melting Point: 203-208 °C
• Boiling Point: 568.2°Cat760mmHg
• Flash Point: 311.5°C
• Appearance: /
• Density: 1.26g/cm³
• Vapor Pressure: 2.83E-15mmHg at 25°C
• Refractive Index: 1.586
• Storage Temp.: Refrigerator
• Solubility: Acetone (Slightly), Chloroform (Very Slightly, Heated), DMSO (Slightly), Methano
• PKA: 12.47±0.70(Predicted)
• CAS DataBase Reference: 11-beta,17-alpha,21-trihydroxy-6-alpha-methylpregn-4-ene-3,20-dione(CAS DataBase Reference)
• NIST Chemistry Reference: 11-beta,17-alpha,21-trihydroxy-6-alpha-methylpregn-4-ene-3,20-dione(1625-39-4)
• EPA Substance Registry System: 11-beta,17-alpha,21-trihydroxy-6-alpha-methylpregn-4-ene-3,20-dione(1625-39-4)

Safety Data

• Hazardous Substances Data: 1625-39-4(Hazardous Substances Data)

Usage

Chemical Properties

Pale Yellow Solid

Uses

A metabolite of Cortisone (C696500).

InChI:InChI=1/C22H32O5/c1-12-8-14-15-5-7-22(27,18(26)11-23)21(15,3)10-17(25)19(14)20(2)6-4-13(24)9-16(12)20/h9,12,14-15,17,19,23,25,27H,4-8,10-11H2,1-3H3/t12-,14-,15-,17-,19+,20-,21-,22-/m0/s1

Synthetic route

5,11β,17,21-tetrahydroxy-6β-methyl-5α-pregnane-3,20-dione (76338-56-2) → 11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4)

Conditions	Yield
With sodium hydroxide

21-acetoxy-11β,17-dihydroxy-6α-methyl-pregn-4-ene-3,20-dione (1625-11-2) → 11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4)

Conditions	Yield
Hydrolysis;

21-acetoxy-11β-hydroxy-6α-methyl-pregna-4,17(20)c-dien-3-one (3386-05-8, 14423-18-8, 75110-33-7) → 11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: diacetoxy-phenyl-iodan; OsO4; pyridine / Reagens 4: tert-Butylalkohol 2: Hydrolysis View Scheme

3,3;20,20-bis-ethanediyldioxy-6β-methyl-5α-pregnane-5,11β,17,21-tetraol (6726-27-8) → 11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: aqueous H2SO4; methanol 2: aqueous methanol.NaOH View Scheme

3,3;20,20-bis-ethanediyldioxy-5,6α-epoxy-5α-pregnane-11β,17,21-triol (76338-55-1) → 11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: diethyl ether; tetrahydrofuran 2: aqueous H2SO4; methanol 3: aqueous methanol.NaOH View Scheme

Methylprednisolone (83-43-2) → 11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4)

Conditions	Yield
With hydrogen; Wilkinson's catalyst In ethanol; ethyl acetate at 20℃; under 760.051 Torr; for 168h;
With hydrogen; Wilkinson's catalyst In ethanol; ethyl acetate at 20℃; under 760.051 Torr; for 168h;
With hydrogen; Wilkinson's catalyst In ethanol; ethyl acetate at 20℃; under 760.051 Torr; for 168h;

17-hydroxy-pregn-4-ene-3,11,20-trione (1882-82-2) → 11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4)

Conditions

Yield

Multi-step reaction with 8 steps 1: toluene-4-sulfonic acid / dichloromethane; water 2: N-methylaniline; hydrogenchloride / tetrahydrofuran 3: hydrogenchloride; palladium on activated charcoal / ethanol; cyclohexene 4: toluene-4-sulfonic acid / dichloromethane 5: sodium tetrahydroborate / methanol 6: hydrogenchloride 7: iodine; calcium chloride; calcium oxide / methanol 8: sodium hydroxide; potassium acetate / methanol; N,N-dimethyl-formamide View Scheme

C22H28O4 → 11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4)

Conditions	Yield
Multi-step reaction with 6 steps 1: hydrogenchloride; palladium on activated charcoal / ethanol; cyclohexene 2: toluene-4-sulfonic acid / dichloromethane 3: sodium tetrahydroborate / methanol 4: hydrogenchloride 5: iodine; calcium chloride; calcium oxide / methanol 6: sodium hydroxide; potassium acetate / methanol; N,N-dimethyl-formamide View Scheme

11-oxomedroxyprogesterone (82332-00-1) → 11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: toluene-4-sulfonic acid / dichloromethane 2: sodium tetrahydroborate / methanol 3: hydrogenchloride 4: iodine; calcium chloride; calcium oxide / methanol 5: sodium hydroxide; potassium acetate / methanol; N,N-dimethyl-formamide View Scheme

C26H38O6 → 11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium tetrahydroborate / methanol 2: hydrogenchloride 3: iodine; calcium chloride; calcium oxide / methanol 4: sodium hydroxide; potassium acetate / methanol; N,N-dimethyl-formamide View Scheme

C26H40O6 → 11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogenchloride 2: iodine; calcium chloride; calcium oxide / methanol 3: sodium hydroxide; potassium acetate / methanol; N,N-dimethyl-formamide View Scheme

11β,17-dihydroxy-6α-methyl-pregn-4-ene-3,20-dione (7055-53-0) → 11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: iodine; calcium chloride; calcium oxide / methanol 2: sodium hydroxide; potassium acetate / methanol; N,N-dimethyl-formamide View Scheme

C22H31IO4 → 11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4)

Conditions	Yield
With potassium acetate; sodium hydroxide In methanol; N,N-dimethyl-formamide

HYDROCORTISONE (50-23-7) → 11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4)

Conditions

Yield

Multi-step reaction with 8 steps 1: toluene-4-sulfonic acid / ethanol / 40 - 45 °C 2: N-methylaniline; hydrogenchloride / tetrahydrofuran 3: hydrogenchloride; palladium on activated charcoal / ethanol; cyclohexene 4: toluene-4-sulfonic acid / dichloromethane 5: sodium tetrahydroborate / methanol 6: hydrogenchloride 7: iodine; calcium chloride; calcium oxide / methanol 8: sodium hydroxide; potassium acetate / methanol; N,N-dimethyl-formamide View Scheme

C23H32O4 → 11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4)

Conditions

Yield

Multi-step reaction with 7 steps 1: N-methylaniline; hydrogenchloride / tetrahydrofuran 2: hydrogenchloride; palladium on activated charcoal / ethanol; cyclohexene 3: toluene-4-sulfonic acid / dichloromethane 4: sodium tetrahydroborate / methanol 5: hydrogenchloride 6: iodine; calcium chloride; calcium oxide / methanol 7: sodium hydroxide; potassium acetate / methanol; N,N-dimethyl-formamide View Scheme

6-methine hydrocortisone → 11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4)

Conditions	Yield
With 5%-palladium/activated carbon In chloroform; cyclohexene at 45 - 60℃; Solvent;	72.8 g

11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4) → 6α-methyl-4-androstene-3,11,17-trione (119677-09-7)

Conditions	Yield
With chromium(VI) oxide; water In acetic acid for 1h; Ambient temperature;	70%

11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4) → 11β,17-dihydroxy-6α-methyl-pregn-4-ene-3,20-dione (7055-53-0)

Conditions	Yield
ueber mehrere Stufen;

11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4) → 21-fluoro-11β,17-dihydroxy-6α-methyl-pregn-4-ene-3,20-dione (387-64-4)

Conditions	Yield
ueber mehrere Stufen;

11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4) → 17,21-dihydroxy-6α-methyl-pregn-4-ene-3,11,20-trione (1746-38-9)

Conditions	Yield
With pyridine; N-bromoacetamide

1,1,1-trimethoxybutane (43083-12-1) + 11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4) → 11β-hydroxy-17,21-(1-methoxybutylidenedioxy)-6α-methyl-4-pregnene-3,20-dione (83625-21-2)

11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4) → 11β,17-dihydroxy-21-methoxyacetoxy-6α-methyl-4-pregnene-3,20-dione

11β,17α,21-trihydroxy-6α-methylpregna-4-ene-3,20-dione (1625-39-4) + acetic anhydride (108-24-7) → 21-acetoxy-11β,17-dihydroxy-6α-methyl-pregn-4-ene-3,20-dione (1625-11-2)

Conditions	Yield
With pyridine In ethyl acetate at 20 - 55℃;

Upstream product

• 76338-56-2 5,11β,17,21-tetrahydroxy-6β-methyl-5α-pregnane-3,20-dione 
• 1625-11-2 21-acetoxy-11β,17-dihydroxy-6α-methyl-pregn-4-ene-3,20-dione 
• 3386-05-8 21-acetoxy-11β-hydroxy-6α-methyl-pregna-4,17(20)c-dien-3-one 
• 6726-27-8 3,3;20,20-bis-ethanediyldioxy-6β-methyl-5α-pregnane-5,11β,17,21-tetraol 
• 76338-55-1 3,3;20,20-bis-ethanediyldioxy-5,6α-epoxy-5α-pregnane-11β,17,21-triol 
• 83-43-2 Methylprednisolone 
• 1882-82-2 17-hydroxy-pregn-4-ene-3,11,20-trione 
• 82332-00-1 11-oxomedroxyprogesterone 
• 7055-53-0 11β,17-dihydroxy-6α-methyl-pregn-4-ene-3,20-dione 
• 50-23-7 HYDROCORTISONE 

Downstream Products

• 1625-11-2 21-acetoxy-11β,17-dihydroxy-6α-methyl-pregn-4-ene-3,20-dione 
• 387-64-4 21-fluoro-11β,17-dihydroxy-6α-methyl-pregn-4-ene-3,20-dione 
• 7055-53-0 11β,17-dihydroxy-6α-methyl-pregn-4-ene-3,20-dione 

Relevant articles and documents

Preparation method of 6a-methyl hydrocortisone

The invention provides a preparation method of 6a-methyl hydrocortisone. The preparation method comprises the steps that hydrocortisone prepared from 4-androstene-3,17-dione (called as 4AD for short) is adopted as a raw material to generate an acid catalytic reaction with triethyl orthoformate in an organic solvent, and etherate 3-ether enol hydrocortisone is obtained; the etherate generates a Manlixi reaction with N-methylaniline and formaldehyde in an organic solvent, and a methylene product 6-methylene hydrocortisone is obtained; the methylene product generates a catalytic hydrogenation reaction in an organic solvent, and 6a-methyl hydrocortisone is obtained. Compared with a production method achieved by taking a mold removal product obtained by processing diosgenin as a raw material, the method for producing 6a-methyl hydrocortisone has the advantages that raw material sources are wide, the processes are economical and environmentally friendly, production operation is easy and convenient, the synthetic route is short, and the product yield is high; by producing 6a-methyl hydrocortisone through the method, the production cost is reduced by 40%-50% compared with a traditional method; the solvents used in production can be recycled and cyclically reused, and implementation of industrialized production is promoted.

NOVEL COMPOUNDS

The present invention provides compounds of formula (I) wherein n, p, R1, R2, X1, X2, X3, X4, X5, R3a, R3b, R4, R5 and R6 are as defined in the specification, a process for their preparation, pharmaceutical compositions containing them and their use in therapy.

Process and intermediates for the preparation of 17 alphahydroxyprogesterones and corticoids from an enol steroid

This invention discloses an improved process for the production of corticoids from 17α-hydroxy steroids utilizing peroxymonosulfate.