| Identification | Back Directory | [Name]
cortivazol | [CAS]
1110-40-3 | [Synonyms]
Altim
Diaster
Idaltin
Dilaster
NSC-80998
cortivazol
Cortivazol DISCONTINUED
6,16α-DiMethylpregna-4,6-diene-11
11β,17α,21-Trihydroxy-6,16α-diMethyl-2'-phenylpregna-
2,4,6-trieno[3,2-c]pyrazol-20-one 21-Acetate
(11β,16α)-21-(Acetyloxy)-11,17-dihydroxy-6,16-diMethyl-2'-phenyl-2'H-pregna-2,4,6-trieno[3,2-c]pyrazol-20-one
2'H-Pregna-2,4,6-trieno[3,2-c]pyrazol-20-one, 21-(acetyloxy)-11,17-dihydroxy-6,16-dimethyl-2'-phenyl-, (11β,16α)- | [EINECS(EC#)]
214-175-8 | [Molecular Formula]
C32H38N2O5 | [MDL Number]
MFCD00867442 | [MOL File]
1110-40-3.mol | [Molecular Weight]
530.661 |
| Chemical Properties | Back Directory | [Melting point ]
160-165° and 229-230° | [alpha ]
D23 +14° (CHCl3) | [Boiling point ]
686.0±55.0 °C(Predicted) | [density ]
1.33±0.1 g/cm3(Predicted) | [pka]
12.43±0.70(Predicted) |
| Hazard Information | Back Directory | [Originator]
Diaster,Diamant,France,1972 | [Uses]
Glucocorticoid. | [Definition]
ChEBI: Cortivazol is a steroid. It derives from a hydride of a pregnane. | [Manufacturing Process]
To a suspension of 25.0 g of 11β,17α,21-trihydroxy-6,16α-dimethyl-4,6-
pregnadiene-3,20-dione in 1.5 liters of alcohol-free chloroform cooled to about
5°C in an ice bath is added with constant stirring 750 ml of cold, concentrated
hydrochloric acid and then 750 ml of formalin (low in methanol). The mixture
is removed from the ice bath and stirred at room temperature for 7 hours.
The layers are separated and the aqueous phase is back-extracted twice with
chloroform. The combined organic layers are washed twice with a 5% solution
of sodium bicarbonate, and twice with a saturated salt solution. The solution is
dried over magnesium sulfate and evaporated to dryness under reduced
pressure.The layers are separated and the aqueous phase is back-extracted twice with
chloroform. The combined organic layers are washed twice with a 5% solution
of sodium bicarbonate, and twice with a saturated salt solution. The solution is
dried over magnesium sulfate and evaporated to dryness under reduced
pressure.
The residue is triturated with methanol to afford a crystalline solid. This
material contains no detectable amount of starting material by paperstrip
chromatography but shows two UV absorbing spots near the solvent front
(methanol-formamide 2:1 vs benzene-n-hexane 1:1). An aliquot is
recrystallized three times from a mixture of benzene and n-hexane to give
17α,20,20,21-bis(methylenedioxy)-11β-hydroxy-6,16α-dimethyl-4,6-
pregnadiene-3-one which is used in the subsequent step of the synthesis
without further purification.
17α,20,20,21-bis(methylenedioxy)-11β-hydroxy-6,16α-dimethyl-4,6-
pregnadiene-3-one (500 mg) is dissolved in 25 cc of benzene and then about
5 cc of benzene is removed by distillation at normal pressure. The resulting
solution is cooled to room temperature. Then 0.75 cc of freshly distilled ethyl
formate is added. The air in the system is replaced with nitrogen and 150 mg
of sodium hydride (as a 57% dispersion in mineral oil) is added. The mixture
is stirred under nitrogen at room temperature for three hours. Then 15 cc of a
saturated aqueous solution of sodium dihydrogen phosphate is added and the
product is extracted into ether
.
The ether extracts are extracted with 2 N sodium hydroxide and the sodium
hydroxide extracts are acidified with sodium dihydrogen phosphate and
extracted again into ether. The ether extract is evaporated to dryness to give
about 500 mg of a crude product. From the ether solution there is obtained
about 290 mg of yellow crystals, MP 220° to 236°C which is 17α,20,20,21-
bis(methylenedioxy)-11β-formyloxy-2-hydroxy-methylene-6,16α-dimethyl-4,6-
pregnadiene-3-one. The analytical sample is recrystallized from ethyl acetate
and has a melting point of 249° to 255°C, [α]D27 -217°, I R 5.81 and 8.37
μm. From the mother liquor is obtained about 127 mg of 17α,20,20-21-
bis(methylenedioxy)-11β-hydroxy-2-hydroxymethylene-6,16α-dimethyl-4,6-
pregnadiene-3-one. The analytical sample is recrystallized from ether and has
a melting point of 200° to 204°C, [α]D27 -197°, IR 6.05 to 6.2 and 6.4 μ.
The 17α,20,20,21-bis(methylenedioxy)-11β-hydroxy-2-hydroxymethylene-
6,16α-dimethyl-4,6-pregnadiene-3-one (1.19 g) is dissolved in 25 cc of
ethanol. 300 mg of phenyl hydrazine is added and the mixture is refluxed
under nitrogen for one hour. About 25 cc of water is added. The product is
then extracted into 150 cc of ether. The extracts are washed with 2N HCl, with
saturated sodium bicarbonate, water and saturated sodium chloride solution,
and then dried over sodium sulfate and evaporated to dryness to give about
1.2 g of crude product. On crystallization from ether there is obtained as a
major component the 17α,20,20,21-bis(methylenedioxy)-11β-hydroxy-6,16α-
dimethyl-2'-phenyl-4,6-pregnadieno-[3,2-c] pyrazole.
17α,20,20,21-bis(methylenedioxy)-11β-hydroxy-6,16α-dimethyl-2'-phenyl-
4,6-pregnadieno[3,2-c] pyrazole (430 mg), is heated on a steam bath under
nitrogen with 40 cc of a 60% aqueous solution of formic acid for about 30
minutes. About 40 cc of water is added and the mixture is then extracted into
200 cc of chloroform. The chloroform solution is washed with water, saturated
1136 Creatinolfosfate
sodium bicarbonate solution and water, then dried over sodium sulfate and
evaporated under vacuum to give 430 mg of crude product. This is dissolved
in 60 cc of absolute methanol, and 0.1 equivalent of sodium methoxide in
methanol is added.
The mixture is stirred under nitrogen at room temperature for 15 minutes. It
is then acidified with acetic acid and the solvent is removed under vacuum at
room temperature. About 20 cc of water is added and the product is extracted
into 150 cc of ethyl acetate. The ethyl acetate solution is washed with
saturated sodium bicarbonate and then with water. It is then dried over
sodium sulfate and taken to dryness to give an amorphous solid.
The crude product obtained above is dried in high vacuum and then dissolved
in 4 cc of pyridine. About 3 cc of acetic anhydride is added. The mixture is
then heated on the steam bath for about 15 minutes and then evaporated to
dryness in vacuo. About 20 cc of water is added. The product is then
extracted into 150 cc of ethyl acetate, washed with saturated sodium
bicarbonate solution and water, and dried over sodium sulfate. The solvent is
removed in vacuo to give a residue which is crystallized from ethyl acetatebenzene to yield about 250 mg of 11β,17α,21-trihydroxy-6,16α-dimethyl-20-
oxo-2'-phenyl-4,6-p
| [Therapeutic Function]
Glucocorticoid |
|
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Energy Chemical
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http://www.energy-chemical.com |
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