KR810000582B1 - Process for the preparation of corticoid 17-(alkyl catbonates) - Google Patents

Abstract

Corticoid 17-(alkylcarbonates) (I; A = CH2, CH(OH), C=O, C(OH)H; Y = H, F, Cl; Z = H, Cl, F, methyl; R1 = H, acyl, carbonyloxyalkyl, aliphatic or aromatic sulfonic ester; R2 = C1-8 alkyl; R3 = H, or -position methy1, F), useful as antiphlogistic agent, were prepd. by reaction of compd.(III) and carboxylic halide at 21-position. The intermediate.(III) was prepd. by hydrolysis of compd.(II).

Description

Process for preparing corticosteroid 17- (alkyl carbonates)

It relates to a process for the preparation of novel steroid 17- (alkyl carbonates) of the general formula (I) which is useful as an anti-inflammatory agent of the present invention.

또는 C=O 그룹을 나타내거나, 만약 9,11-위치에 이중결합이 존재하면 C-H 그룹을 나타내며 Y는 수소, 불소 또는 염소를 나타내며 Z는 수소, 염소, 불소 또는 메틸 그룹을 나타내고 R₁은 수소, 다음 일반식(a)의 아실기In the above structural formula A is

Or a C═O group, or if a double bond is present at the 9,11-position, represents a CH group, Y represents hydrogen, fluorine or chlorine, Z represents hydrogen, chlorine, fluorine or methyl group and R ₁ represents hydrogen , Acyl group of the following general formula (a)

기를 나타내며 여기서 R' 및 R＂ 는 동일하거나 상이하며 수소 또는 탄소수 1 내지 4의 알킬기이거나, R' 및 R＂는 질소와 함께 5 내지 7원소의 포화 복소환 구조를 나타낸다).Wherein R ₄ is hydrogen or a straight or branched aliphatic hydrocarbon group of 1 to 10 carbon atoms, or an alicyclic hydrocarbon group of 3 to 8 carbon atoms and n is an integer of 0 to 4 or if n ≠ 0, then R ₄ is halogen or

And R 'and R' are the same or different and are hydrogen or an alkyl group having 1 to 4 carbon atoms, or R 'and R' together with nitrogen represent a saturated heterocyclic structure of 5 to 7 elements.

Moreover, the carbonyl oxyalkyl group of following General formula (b)

Wherein n and R ₄ are as defined above and R ₄ ≠ H when n is 0 and R ₄ may represent only halogen when n is 2-4.

Or aliphatic or aromatic sulfonic acid esters of the general formula (C)

은 3-데옥소-스테로이드 골격의 2와 3 위치에 축합되고 두 질소 원자중의 한 원자에 탄소수 1 내지 4의 알킬그룹, 또는 임의로 할로겐 치환된 페닐 그룹을 지닐 수 있는 피라졸 환을 나타낸다.Wherein R ₅ is alkyl having 1 to 4 carbon atoms, phenyl, methylphenyl, ethylphenyl, fluorophenyl, bromophenyl or chlorophenyl; R ₂ is a straight or branched alkyl group having 1 to 8 carbon atoms and R ₃ is Hydrogen, methyl in the α or β-position, fluorine, or a methyl group optionally substituted with one or two fluorine atoms and represent 1,2- and / or 2,3- and / or 6,7- and ( Or), additional double bonds may be present at the 9,11-position,

Denotes a pyrazole ring which is condensed at positions 2 and 3 of the 3-deoxo-steroidal skeleton and may have an alkyl group of 1 to 4 carbon atoms, or an optionally halogen substituted phenyl group, at one of the two nitrogen atoms.

기를 함유하는 카복실산 할라이드 또는 카복실산 무수물과 또는

기를 함유하는 할로게노포르메이트와 또는

기를 함유하는 지방족 또는 방향족 설폰산 할라이드류와 21-위치에서 반응시켜 일반식(I)의 스테로이드 17-(알킬 카보네이트)류를 제조한다. 단 R≠H일 때는 11위치의 OH기를 통상의 방법으로 케토그룹으로 산화시킨다.In the present invention, the corticosteroid 17,21- (dialkyl orthocarbonates) of the following general formula (II) is hydrolyzed to obtain steroid 17- (monoalkyl carbonates) of the following general formula (III),

With carboxylic acid halides or carboxylic anhydrides containing groups or

With halogenoformates containing groups or

The steroid 17- (alkyl carbonate) of the general formula (I) is prepared by reacting an aliphatic or aromatic sulfonic acid halide containing a group at the 21-position. However, when R ≠ H, the OH group at the 11 position is oxidized to the keto group by a conventional method.

, R₂, R₃, R₄및 R₅는 상기에서 정의된 바와같고 1, 2-및(또는) 2,3-및(또는) 6,7-및(또는) 9,11-위치에 이중결합이 존재할 수 있다. 단 R₂, R₄및 R₅는 다음의 기가 바람직하다.Wherein A, Y, Z,

, R ₂ , R ₃ , R ₄ and R ₅ are as defined above and are doubled in the 1, 2- and / or 2,3- and / or 6,7- and / or 9,11-positions. There may be a bond. However, R ₂ , R ₄ and R ₅ are preferably the following groups.

R ₂ is preferably an alkyl group having 1 to 5 carbon atoms, R ₄ is preferably hydrogen, an alkyl having 1 to 10 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, or a fluorine, chlorine, bromine or piperidine group if n ≠ 0, and R ₅ Is methyl, ethyl, propyl, phenyl, substituted phenyl groups (in each case the substituents are substituted in the P-position).

Steroids 17α, 21- (dialkyl ortho carbonates) of the general formula (II) used as starting materials in the present invention are known compounds and may be prepared according to the methods set forth in German Patent Application No. 1,668,079. The starting materials used are the following 17α, 21-dihydroxy-steroids and 17α, 21- (dialkylorthocarbonates) of the corticoids: cortisone, hydrocortisone, the substrate of S. Leistein, prednisolone prednisolone, 6α-methyl predinisolone, 16α-or 16β-methylprednisolone, 9α-fluoro- or 9α-chloro-prednisolone, 16-methyleneprednisolone, 6α, 9α-difluoroprednisolone, 6α-methyl-9α-fluoro- Prednisolone, 6α-fluoro-prednisolone, 9α-fluoro-16α-methyl-prednisolone, 9α-fluoro-prednisolone, 9α-fluoro-16α-methyl-prednisolone, 9α-fluoro-prednisolone, 9α-fluoro- 16-methyl-prednisolone, 6-α-fluoro-16β-methyl-prednisolone, 6α-fluoro-16α-methyl-prednisolone, 6α-fluoro-16-methylene-prednisolone, 6α, 9α-difluoro-16β Methyl-prednisolone, 6α, 9α-difluoro-16β-methyl-prednisolone, 6α, 9α-difluoro-16-methylene-prednisolone, 9α-fluoro-6α, 16α-dimethyl-prednisolone, 9α, 16α-difluoro-prednisolone , 17α, 21-dihydroxy Δ4 (5), 9 (11) -pregnadiene-3,20-dione, 17α, 21-dihydroxy-9β, 11β-oxido-Δ ⁴ -pregnene -3,20-dione, 17α, 21-dihydroxy-9α, 11β-dichloro-Δ ^1.4 -pregnadiene-3,20-dione, 17α, 21-dihydroxy-Δ4 (5), 6 (7) -pregnadiene-3,20-dione, deoxycorticosterone, corticosterone, 16α-methyl-corticosterone, 9α-fluoro-16α-methyl-corticosterone, 6α, 9α- Difluoro-16α-methyl-corticosterone, 6α-fluoro-16α-methyl-corticosterone, 6,16α-dimethyl-4,6-fragnadiene-11β, 17α, 21-triol- [ 3,2-c] -2'-phenylpyrazole and -2'-P-fluorophenylpyrazole and homologues substituted with fluorine at the 9a-position; A and (or) it can be used in the koreutikoyi teuryu containing chlorine atoms matching the coordinates corresponding to the place of a and (or) 11β- hydroxy group-fluoro 9α-.

In the first reaction step of the preparation process, that is, the steroid 17α, 21- (dialkylorthocarbonate) s are proton catalyzed to obtain the corresponding steroid 17α- (monoalkylcarbonate) -21-hydroxy compound, formic acid, acetic acid, Carboxylic acids such as propionic acid, butyric acid, valeric acid, oxalic acid, maleic acid, fumaric acid, succinic acid or adipic acid, or P-toluenesulfonic acid, benzenesulfonic acid, P-, 0- or m-chloro- or bromo-benzene Organic sulfonic acids such as sulfonic acid or inorganic acids such as hydrochloric acid, sulfuric acid, carbonic acid and nitric acid are used. The process of obtaining the desired steroid 17α- (monoalkylcarbonate) -21-hydroxy compound is more specific as the pH approaches 7, i.e., the weaker the acidity.

This is not the same as in the case of structurally similar 17α, 21-steroid-carboxylic acid orthoesters, because the alkoxy ligands which are linked to the carbon atoms of the orthocarboxylic acid group are equivalent, and therefore in terms of the preferred separation of the ortho esters, the latter This is even more surprising because it is not possible to promote or induce regional selectivity related to the traitors. To adjust the pH to the desired value with the above acid, active organic solvents such as water and / or alcohols, linear or cyclic ethers, esters, dialkylformamide dialkylsulfoxides, hexamethylphosphoric acid and triamides It is appropriate to add, and in addition to the dilution effect, there may be a catalytic or regional selection effect.

The reaction process was performed by thin layer chromatography, and an appropriate amount of a steroid 17α- (monoalkyl carbonate) -21-hydroxy compound was formed by a thin layer diagram, and this substance was not used as an steroid 17α-hydroxy-21 (monoalkyl). It is advantageous to stop the reaction by neutralizing it with ammonia or by adjusting the pH to 7 or more when it starts to isomerize with the carbonate) compound.

Preferably, the corticoid 17,21- (orthoalkyl carbonate) is dissolved in carboxylic acids, such as acetic acid, propionic acid, about 0.1-1% water is added and the mixture is brought to 0 ° C. to the boiling point temperature of the acid or solvent used. React while raising over 8 hours. According to the thin layer chromatography diagram, when the desired amount is formed, the reaction mixture is added to water or sodium chloride solution with stirring, the resulting mixture is neutralized with aqueous ammonia or weak base and the resulting precipitate is filtered off or the reaction mixture is organic. After extraction in a conventional manner with a solvent and then evaporation of the extract and recrystallization of the resulting product, the starting material is still detected in the thin layer chromatography diagram, or if 21- (alkyl progressivenate) is already detected on silica gel or aluminum oxide. Thin layer chromatography.

21-hydroxy group, depending on which of 21- (alkyl carbonate), 21- (carboxylic acid ester) or 21- (alkyl- or aryl-sulfonic acid ester) of the basic corticoid 17- (alkyl carbonate) should be prepared Can be reacted with these intended acylating agents:

(R₄는 일반식 I에서 정의된 바와 같다)의 알킬 클로로포르메이트가 바람직하게 사용된다. 바람직하게는 메틸 클로로포르메이트, 에틸클로로 포르메이트, 프로필 클로로포르메이트 또는 부틸클로로 포르메이트가 사용된다.a) General formula for preparing 21- (alkyl carbonates)

Alkyl chloroformates of which R ₄ is as defined in formula I are preferably used. Preferably methyl chloroformate, ethylchloro formate, propyl chloroformate or butylchloro formate is used.

(Hal는 Cl, Br 또는 I 이며 R₄는 일반식(I)에서 정의된 바와 같다)의 카복실산 할라이드나 일반식(OC-(CH₂)_n-R₄)₂O(R₄는 일반식(I)에서 정의된 바와같다)의 카복실산 무수물이 바람직하게 사용된다. 예를들면 아세틸 클로라이드 또는 아세트산 무수물, 프로피오닐 클로라이드 또는 프로피온산 무수물, 부티릴 클로라이드 또는 부티르산 무수물, 발러릴 클로라이드 또는 발레르산 무수물, 사이클로 프로판카르복실산 클로라이드, 사이클로펜틸 프로피오닐 클로라이드 또는 오에난틸 클로라이드 등이 사용될 수 있다.b) General formula for preparing 21- (carboxylic acid ester) s

(Hal is Cl, Br or I and R ₄ is as defined in formula (I)) or a carboxylic acid halide of formula (OC- (CH ₂ ) _n -R ₄ ) ₂ O (R ₄ is a general formula ( Carboxylic anhydrides), as defined in I), are preferably used. For example, acetyl chloride or acetic anhydride, propionyl chloride or propionic anhydride, butyryl chloride or butyric anhydride, valeryl chloride or valeric anhydride, cyclo propanecarboxylic acid chloride, cyclopentyl propionyl chloride or enanthyl chloride may be used. Can be.

C) To prepare 21- (sulfonic acid esters), sulfonic acid halides of the general formula Cl-SO ₂ -R ₅ (R ₅ is as defined in formula (I)) can be used. Preferably methane sulfonyl chloride and 0-, m-, or P-toluene sulfonyl chloride are used.

In the second step, the steroid component is added to an ether such as dioxane, tetra hydrofuran, diglyme, or an inert solvent such as halogenated hydrocarbons such as benzene, toluene, cyclohexane, methylene chloride, chloroform or mixtures of these solvents. Dissolve.

To remove the hydrogen halide acid generated during the reaction, tertiary bases such as 1 to 1000 molar equivalents of pyridine, quinoline, triethyl amine and dimethyl aniline are added. However, inorganic bases such as sodium bicarbonate and calcium carbonate are also used for the purpose of acid removal. Then, 1 to 200 molar equivalents (preferably 1 to 3 molar equivalents) of the acylating agent dissolved in the solvent are added dropwise at a temperature between the boiling point of the solvent used (preferably 0 ° to 25 ° C). Next, it is allowed to stand for 1 to 120 hours at a temperature between -40 ° C and the boiling point of the solvent (preferably 0 ° C to 25 ° C).

When carboxylic anhydride is used as the acylating agent, it is advantageous to carry out the reaction without adding a solvent. Generally, it is sufficient to add an organic base such as pyridine to the acid anhydride used in excess.

To complete the above reaction mixture is poured into water and sodium bicarbonate is optionally added thereto, after which the reaction product does not precipitate in crystalline form until long after standing.

The oily reaction product is shaken with a suitable extractant and concentrated by evaporation. If desired, the reaction product is isolated or purified by recrystallization or chromatography.

It is also sufficient to purify the reaction product by soaking it in an organic solvent that dissolves the reaction product as little or as little as possible, such as diethyl ether, cyclo hexane or mixtures thereof.

The hydroxyl group at the 11 position can be oxidized to the keto group by conventional methods. Preferably the oxidation reaction is carried out using chromium trioxide in acid medium and inert organic solvents.

The product of this recipe has useful pharmacological properties. In particular, they have a very strong local anti-inflammatory action and the ratio of local anti-inflammatory action to systemic anti-inflammatory action is advantageous as can be inferred from pharmacological standard tests.

The product can be used in the form of suspensions, ointments, creams, sprays and the like for the treatment of inflammatory skin diseases caused by various causes of shrinkage. For topical use, it can be injected intraarticular in the form of a crystalline spray. Due to the favorable rate of local anti-inflammatory activity to the whole body of these compounds, they are particularly advantageous for topical treatment because they only cause substantially minor systemic side effects even at high doses or even during long-term treatment. In addition, the compound is much more stable against acids than cyclic corticoid 17,21-ortho carbonates. This fact is of critical importance for the therapeutic use of the compounds according to the invention.

The following general attention is directed to the examples given below.

Melting point was determined by Tottoli device (Messrs, Buchi) and not corrected.

IR spectra (in KBr) were recorded on a photometer with Perkin Elmer 521 diffraction grating spectra and only characteristic bands were measured in each case. UV spectra (in methanol) were recorded with Beckmun Dk1A spectrophotometer and measurements by mass spectroscopy (MS) were performed using the MS9 device (Messrs AEl).

For TLC, pre-made silica gel F254 plate (Messrs Merck) was used.

Unless stated otherwise, the solvents used are methylene chloride; Methanol = 19: 1 solvent and in each case only developed once. The spot was manifested by spraying 10% methanolic sulfuric acid and heating to 100 ° C. and the Rf value should be understood as a relative figure. Silica gel 60 (Messrs Merck) having a particle size of 0.063 to 0.2 mm was used for column chromatography.

Example 1

a) 120 ml of glacial acetic acid and 0.6 ml of aqueous solution containing 3 g of dexamethasone 17,21- (diethylorthocarbonate) are allowed to stand at 22 ° C for 5 hours. Tracing the reaction by TLC showed that over this time there was an optimal amount of dexamethasone 17- (ethyl carbonate) desired. When the reaction mixture is added to 1.5 L of water and the pH is adjusted to 5 with ammonia water, crystalline precipitate is separated out. Filtration, washing with water and drying gave 1.8 g of dexamethasone 17- (ethyl carbonate) (melting point: 154 °, Tottoli) after warming. The remaining aqueous filtrate is extracted with methylene chloride. Distillation of the solvent leaves a foamy residue which is crystallized with diisopropyl ether to give 1.2 g of dexamethasone 17- (ethyl carbonate) (melting point: 152 °). Combine the two samples of 1.8g and 1.2g above and recrystallize with ethanol. Melting point: 156 ° C. (Tottoli).

Characteristic IR band: 3440, 2940, 2880, 1735, 1720, 1660, 1610, 1265cm ^-1

에서 분자량 피크 : 464Mass Spectrum: M

Molecular weight peak at: 464

TLC: Rf = 0.43 (CH ₂ Cl ₂ : CH ₃ OH 19: 1)

b) 250 ml of glacial acetic acid containing 4 g of dexamethasone 17,21- (dimethylorthocarbonate) and 1 ml of an aqueous solution were allowed to stand at 20 ° C. for 15 minutes and then stirred and added to a 2.2 L semi-saturated sodium chloride solution. do. Finish treatment similar to that in Example 1a) yields 3.2 g of dexamethasone 17- (methyl carbonate).

Mass spectrum: M ⁺ : 450

TLC: Rf = 0.42

c) 280 ml of glacial acetic acid and 1.2 ml of an aqueous solution containing 4.5 g of dexamethasone 17,21- (di- (n-propyl) ortho carbonate) are allowed to stand at 20 ° C. for 5 hours, and the solution is placed in a 4L semi- Add to saturated sodium chloride solution. The supernatant is decanted from the precipitation of the oil phase and this oil is dissolved in methylene chloride and washed with water. Distillation of the solvent gave 3.3 g of dexamethasone 17- (n-propylcarbonate) in the form of an amorphous foam.

Characteristic IR bands: 3440, 1730, 1655, 1610 and 1240 cm ^-1 .

Mass spectrum: M ⁺ = 476

TLC: Rf = 0.42

d) 4.5 g of dexamethasone 17,21- (di- (n-butyl) orthocarbonate) are reacted as indicated in Example 1) C) to complete the product. Warming with diisopropyl ether yields 2.9 g of dexamethasone 17- (n-butyl carbonate). (Melting point: 92 ° C)

IR: 3430, 1730, 1655, 1605, 1270cm ^-1

e) 4.5 g of dexamethasone 17,21- (di (n-pentyl) ortho carbonate) prepared from dexamethasone and tetra n-pentyl ortho carbonate according to the method of the German Federal Patent No. 1668079 (melting point: 106 ° C.) is reacted as described in Example 1) c) to complete the product. 3.4 g of amorphous dexamethasone 17- (n-pentyl carbonate) are obtained.

IR: 3440, 1735, 1660, 1610, 1275cm ^-1

Example 2

a) 9 ml of dioxane solution containing 1.1 g of ethyl chloroformate is added dropwise to 3 ml of anhydrous dioxane and 4.5 ml of pyridine solution containing 1.4 g of dexamethasone 17- (ethyl carbonate) at 0 ° C. . After 5 hours of stirring at 0 ° C., the mixture is added to 300 ml of half-saturated aqueous sodium chloride solution. The reaction mixture was extracted with methylene chloride, the organic layer was washed with water and the solvent was evaporated in vacuo to yield 1.4 g of dexamethasone 17,21-bis- [ethyl carbonate]. (Melting point: 202 to 204 ° C).

TLC shows that the product still shows strong spots at Rf = 0.57 and weak spots at Rf = 0.47 and 0.33.

In order to obtain a high purity product, the reaction product is separated by chromatography on silica gel (3x10 cm column) using acid-free methylene chloride as an adsorption eluent.

Fractions identified on the TLC diagram as the desired reaction product (Rf = 0.57) are collected and crystallized from ethanol / ether.

1.2 g of dexamethasone 17,21-bis- (ethyl carbonate) are obtained. (Melting point: 210 ° C).

TLC: Rf = 0.57 (secondary spots not shown).

IR: 3420, 1735, 1660, 1610, 1260 cm ^-1 .

b) 1.4 g of dexamethasone 17- (ethyl carbonate) was reacted with 1.1 g of methylchloroformate instead of ethyl chloroformate as in Example 2) a) and finished and then dexamethasone 17- (ethyl carbonate) -21- (methyl carbonate) is obtained.

IR: 3420, 1740, 1665, 1615, 1260 cm ^-1 .

c) 1.4 g dexamethasone 17- (ethyl carbonate) was reacted with 1.2 g propyl chloroformate instead of ethyl chloroformate as in Example 2) b), and when finished, dexamethasone 17- (ethyl carbonate) -21- (n-propyl carbonate) is obtained.

IR: 3420, 1735, 1660, 1615, 1265 cm ^-1 .

d) 1.4 g of dexamethasone 17- (ethyl carbonate) was reacted with 1.3 g of n-butyl chloroformate instead of ethyl chloroformate as in Example 2) b), and when finished, dexamethasone 17- (ethyl Carbonate) -21- (n-butyl carbonate) is obtained.

IR: 3420, 1735, 1660, 1610, 1265 cm ^-1 .

e) 1.4 g dexamethasone 17- (ethyl carbonate) was reacted with 1.2 g iso-propyl chloro formate instead of ethyl chloroformate as in Example 2) b) and finished to complete dexamethasone 17- (ethyl Carbonate) -21- (isopropyl carbonate) is obtained.

IR: 3420, 1735, 1665, 1615, 1265, 1265 cm ^-1 .

f) 5 ml of methanesulfonyl chloride is added dropwise to 35 ml of anhydrous acetone and 12 ml of anhydrous pyridine solution containing 3 g of dexamethasone 17- (ethyl carbonate) at 0 ° C. The mixture is stirred for 20 hours while gradually increasing the temperature from 0 ° C to 22 ° C, and the reaction mixture is added to water vapor and extracted with methylene chloride. The organic layer is washed and concentrated in vacuo. The residue is chromatographed with methylene chloride with eluent on silica gel (4 x 14 cm column).

TLC collects pure fractions with Rf = 0.62 and crystallizes with ethanol / ether.

2.6 g of dexamethasone 17- (ethyl carbonate) 21-methane sulfonate are obtained (melting point: 193 ° C).

Mass spectrum: M ⁺ = 542

IR: 3430, 1730, 1655, 1610, 1600, 1350, 1265, 1170, 1030 cm ^-1 .

g) 0.3 ml of cyclopropane carboxylic acid chloride is added dropwise to 12 ml of anhydrous pyridine solution containing 1 g of dexamethasone 17- (ethyl carbonate).

Stir at 20 ° C. for 24 hours and add the mixture in water / Nacl solution to filter the resulting precipitate. Yield 1 g. Chromatography with methylene chloride, optionally with 2% methanol, added on silica gel (2x10 cm column) and fractions with Rf = 0.6 were collected and crystallized from ethanol / ether.

730 mg of dexamethasone 17- (ethyl carbonate) -21-cyclopropane carboxylate are obtained (melting point: 219 ° C.).

IR: 3440, 1730, 1660, 1610, 1610, 1260 cm ^-1 .

MS spectrum: M ⁺ = 532

h) 0.26 ml of propionyl chloride is added dropwise to 12 ml of pyridine solution containing 1 g of dexamethasone 17- (ethyl carbonate) at 0 ° C. and the mixture is stirred at 20 ° C. for 3 hours. This mixture is added to water, neutralized with dilute hydrochloric acid, and the precipitated oil is separated and dissolved in methylene chloride. The solution is washed with water, concentrated in vacuo and chromatographed as in Example 2) g) to obtain a residue which is recrystallized from ether.

817 mg of dexamethasone 17- (ethyl carbonate) 21-n-propionate is obtained (melting point: 220-222 ° C.).

TLC: Rf = 0.6

IR: 3450, 1730, 1660, 1610, 1600, 1260 cm ^-1 .

MS spectrum: M ⁺ = 520

i) 1 g dexamethasone 17- (ethyl carbonate) is reacted with acetyl chloride instead of propionyl chloride as in Example 2R) and completed to give dexamethasone 17- (ethyl carbonate) -21-acetate. (Melting point: 236 to 240 ° C)

IR: 3460, 1740, 1660, 1610, 1265 cm ^-1 .

The same product is obtained by standing in the same manner for 4 hours at 20 ° C. using 4 ml of anhydrous acetic acid instead of acetyl chloride.

j) 1 g of dexamethasone 17- (ethyl carbonate) was reacted with 0.3 ml butyryl chloride instead of propionyl chloride as in Example 2) h) and finished and then dexamethasone 17- (ethyl carbonate) -21- Butyrate is obtained (melting point: 202 to 205 ° C).

k) 1 g of dexamethasone 17- (ethyl carbonate) was reacted with 0.4 ml of valeryl chloride instead of propionyl chloride as in Example 2) h) and completed, dexamethasone 17- (ethyl carbonate) -21- Valorate is obtained.

IR: 3460, 1735, 1660, 1610, 1260 cm ^-1 .

1 g of dexamethasone 17- (ethyl carbonate) was dissolved in 1.28 g of 3 ml of anhydrous dioxane in place of cyclopropane carboxylic acid chloride with cyclopentylpropionyl chloride as in Example 2) g) and completed 645 mg Dexamethasone 17- (ethyl carbonate) -21-cyclo-pentyl-propionate of (Melting Point: 202 ° C.) was obtained.

IR: 3440, 1735, 1660, 1600, 1265 cm ^-1 .

MS spectrum: M ⁺ = 588

Example 3

a) 2 ml of dioxane anhydrous solution containing 0.32 ml of methylchloroformate in 6 ml of dioxane anhydride and 4 ml of anhydrous pyridine solution containing 1 g of dexamethasone 17- (ethylcarbonate) with stirring at 0 ° C. Add it down. After stirring for 5 hours at room temperature, the mixture is poured into 300 ml of a half-saturated aqueous sodium chloride solution, and the precipitated crystalline product is filtered off, washed with water and dried. 1.2 g of crude dexamethasone 17.21-bis- [methylcarbonate] was obtained, which was chromatographed with methylene chloride on silica gel (3 x 13 cm column). In TLC, only fractions with Rf = about 0.55 were collected and crystallized with alcohol / ether to give dexamethasone 17.21-bis- (methylcarbonate) (melting point: 250 ° C).

TLC: Rf = 0.55

IR: 3640, 1740, 1655, 1610, 1440, 1275 cm ^-1 .

MS spectrum: M ⁺ = 508

b) 4.5 ml of dioxane containing 700 mg of dexamethasone 17- (methylcarbonate) (which is a single compound according to TLC) while stirring 2.7 ml of dioxane solution containing 550 mg of ethylchloroformate at 0 ° C. And 2.8 ml pyridine solution dropwise. Stirred further at 0 ° C. for 16 hours, and the mixture was added to an aqueous sodium chloride solution, and the precipitated crystalline product was filtered off, dried (710 mg) and recrystallized from acetone / ether. TLC was performed to obtain 630 mg of a single compound of Rf = 0.53, that is, dexamethasone 17- (methylcarbonate) -21-ethylcarbonate (melting point: 249 ° C).

IR: 3460, 1740, 1655, 1610, 1440, 1265 cm ^-1 .

Mass Spectrum: M ⁺ = 522

c) 700 mg dexamethasone 17- (methyl carbonate) instead of ethyl chloroformate 1) 660 mg n-propylchloroformate, 2) 650 mg n-butyl chloroformate, 3) 600 mg iso-propyl chloro When reacted with formate as in Example 3) b) and completed, in each case the corresponding 1) dexamethasone 17- (methylcarbonate) -21- (n-propylcarbonate), 2) dexamethazone 17- (Methylcarbonate) -21- (n-butyl carbonate), 3) dexamethasone 17- (methylcarbonate) -21- (iso-propyl carbonate) and 4) dexamethasone 17- (methylcarbonate) -21- ( Iso-butyl carbonate) is obtained respectively.

d) 3 g of dexamethasone 17- (methyl carbonate) was reacted with methanesulfonyl chloride as in Example 2) f) and completed and 2.4 g of dexamethasone 17- (methyl carbonate) -21-methanesulfonate Is obtained (melting point 210 to 214 ° C (decomposition))

MS spectrum: M ⁺ = 528

e) 1 ml of dioxane solution in which 0.5 ml of cyclopropane carboxylic acid chloride is dissolved is added dropwise with stirring at 0 ° C. in 3 ml of pyridine and 5 ml of dioxane solution containing 600 ml of dexamethasone 17- (methyl carbonate). Stir at 20 ° C. for 5 hours, add this mixture in water / sodium chloride and filter the resulting precipitate. Yield is 510 mg. Chromatography and crystallization with acetone / ether as in Example 2g) afforded dexamethasone 17- (methyl carbonate) -21-cyclopropane carboxylate (melting point: 274 ° C.).

IR: 3460, 1735, 1655, 1610, 1435, 1270 cm ^-1 .

MS spectrum: M ⁺ = 518

f) 1 ml of dioxane solution containing 0.2 ml of propionyl chloride is added dropwise into a 8.4 ml pyridine solution containing 700 mg of dexamethasone 17- (methyl carbonate) at 0 ° C. and stirred at 22 ° C. for 3 hours. . It is added to water, neutralized with dilute hydrochloric acid, the precipitate is filtered off, washed with water and dried. In another batch, the reaction product is obtained as an oil which is separated, dissolved in methylene chloride, washed with water and concentrated in vacuo. In each case the obtained reaction product was chromatographed as in Example 2) g) and recrystallized from acetone / ether to give 550 mg of dexamethasone 17- (methyl carbonate) -21-n-propionate (melting point: 260 ° C.).

IR: 3460, 1735, 1655, 1610, 1435, 1270 cm ^-1 .

MS spectrum: M ⁺ = 506

g) 700 mg dexamethasone 17- (methyl carbonate) to propionyl chloride 1) 0.2 ml acetyl chloride 2) 0.3 ml butyryl chloride 3) 0.4 ml valeryl chloride and 4) 1 ml cyclopentyl propionyl chloride And reacted as in Example 3f) and completed, respectively,

1) dexamethasone 17- (methyl carbonate) -21-acetate,

2) dexamethasone 17- (methyl carbonate) -21-butyrate,

3) dexamethasone 17- (methyl carbonate) -21-balarate and

4) Dexamethasone 17- (methyl carbonate) -21-cyclopentyl-propionate is obtained.

Example 4

a) 1 ml of dioxane solution containing 0.8 ml of methyl chloroformate is added dropwise into 8 ml of dioxane and 7 ml of pyridine solution containing 1 g of hexametazone 17- (n-propyl carbonate) with stirring at 0 ° C. And the reaction mixture is stirred at 22 ° C. for 16 h. It is added to 250 ml of half-saturated aqueous sodium chloride solution and the separated precipitate is filtered off, washed and dried: TLC: Rf = 0.60, in another batch, the precipitate is dissolved in methylene chloride or extracted with methylene chloride. The methylene chloride solution is washed with water and the solvent is distilled off in vacuo leaving a residue. TLC: Rf = 0.60 The yield is 900 mg in each case. The crude product is chromatographed with methylene chloride on silica gel (3x7 cm colour) to obtain pure product. TLC was performed to collect fractions of Rf = 0.60 and crystallize with acetone / ether to yield 720 mg of dexamethasone 17- (n-propyl carbonate) -21- (methyl carbonate) (melting point: 167 ° C).

IR: 3440, 1730, 1655, 1610, 1440, 1265 cm ^-1 .

MS spectrum: M ⁺ = 526

b) 1 g of dexamethasone 17- (n-phoropylcarbonate) instead of methyl chloroformate 1) 0.9 ml ethylchloroformate, 2) 1.0 ml n-propylchloroformate, 3) 1.1 ml n Butylchloroformate, 4) 1.0 ml of isopropyl chloroformate, 5) 1.1 ml of isobutyl chloroformate, 6) 0.8 ml of acetylchloride, 7) 0.8 ml of propionyl chloride, 8) 0.9 ml of Butyryl chloride, 9) 1 ml of valeryl chloride, 10) 1 ml of cyclo propanecarboxylic acid chloride, and 11) 1.3 ml of cyclopentyl propionyl chloride, as in Example 4a), respectively, and in each case the corresponding

1) dexamethasone 17- (n-propyl carbonate) -21-ethyl carbonate,

2) dexamethasone 17- (n-propyl carbonate) -21- (n-propyl carbonate),

3) dexamethasone 17- (n-propyl carbonate) -21- (n-butyl carbonate),

4) dexamethasone 17- (n-propyl carbonate) -21- (n-isopropyl carbonate),

5) dexamethasone 17- (n-propyl carbonate) -21- (isobutyl carbonate),

6) dexamethasone 17- (n-propyl carbonate) -21-acetate,

7) dexamethasone 17- (n-propyl carbonate) -21-propionate,

8) dexamethasone 17- (n-propyl carbonate) -21-butyrate,

9) dexamethasone 17- (n-propyl carbonate) -21-balarate,

10) dexamethasone 17- (n-propyl carbonate) -21-cyclopropene carboxylate,

11) Dexamethasone 17- (n-propyl carbonate) -21-cyclopentylpropionate is obtained.

c) 3 g of dexamethasone 17- (n-propyl carbonate) was reacted with methanesulfonyl chloride as in Example 2f) and completed and determined by acetone / ether to dexamethasone 17- (n-propyl carbonate)- 21-methane sulfonate is obtained.

Example 5

a) 1 g dexamethasone 17- (n-butyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloro formate,

2) 0.8 ml of ethyl chloro formate,

3) 0.9 ml n-propyl chloro formate,

4) 0.9 ml n-butyl chloro formate,

5) 1.0 ml of isopropyl chloro formate,

6) 1.0 ml of isobutyl chloro formate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) Reaction and completion as in Example 4a) with 1.3 ml of cyclopentyl propionyl chloride results in the corresponding

1) dexamethasone 17)-(n-butyl carbonate) -21- (methylcarbonate),

2) dexamethasone 17- (n-butyl carbonate) -21- (ethylcarbonate),

3) dexamethasone 17- (n-butyl carbonate) -21- (n-propylcarbonate),

4) dexamethasone 17- (n-butyl carbonate) -21- (n-butylcarbonate),

5) dexamethasone 17- (n-butyl carbonate) -21- (isopropylcarbonate),

6) dexamethasone 17- (n-butyl carbonate) -21- (isobutyl carbonate),

7) dexamethasone 17- (n-butyl carbonate) -21-acetate,

8) dexamethasone 17- (n-butyl carbonate) -21-propionate,

9) dexamethasone 17- (n-butyl carbonate) -21-butyrate,

10) dexamethasone 17- (n-butyl carbonate) -21-valorate,

11) dexamethasone 17- (n-butyl carbonate) -21-cyclopropane carboxylate and

12) Dexamethasone 17- (n-butyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of dexamethasone 17- (n-butyl carbonate) was reacted with methanesulfonyl chloride as in Example 2f), completed and crystallized with ether to give dexamethasone 17- (n-butyl carbonate) -21- Methanesulfonate is obtained.

Example 6

a) 1 g of dexamethasone 17- (n-pentyl carbonate) instead of methyl chloroformate, respectively

1) 0.8 ml methyl chloroformate,

2) 0.9 ml of ethyl chloroformate,

3) 1.0 ml of n-propyl chloroformate,

4) 1.0 ml of n-butyl chloroformate,

5) 1.0 ml of pentyl chloroformate,

6) 0.8 ml of acetyl chloride,

7) 0.8 ml propionyl chloride,

8) 0.9 ml of varyl chloride and

9) Reacting and completing 1 ml of cyclo propane carboxylic acid chloride as in Example 4a),

1) dexamethasone 17- (n-pentyl carbonate) -21- (methyl carbonate),

2) dexamethasone 17- (valoryl carbonate) -21- (ethyl carbonate),

3) dexamethasone 17- (valoryl carbonate) -21- (n-propylcarbonate),

4) dexamethasone 17- (n-pentyl carbonate),

5) dexamethasone 17- (n-pentyl carbonate) -21- (n-pentylcarbonate),

6) dexamethasone 17- (n-pentyl carbonate) -21-acetate,

7) dexamethasone 17- (n-pentyl carbonate) -21-propionate,

8) dexamethasone 17- (n-pentyl carbonate) -21-valorate and

9) Dexamethasone 17- (n-pentyl carbonate) -21-cyclopropane carboxylate is obtained.

b) 3 g of dexamethasone 17- (n-pentyl carbonate) is reacted with methanesulfonyl chloride as in Example 2f) and the product is complete and dexamethasone 17- (n-pentyl carbonate) -21-methane sulfo Nate is obtained.

Example 7

5.4 g of 6α-fluoro-prednisolone 17α, 21- (diethylorthocarbonate) are stirred at 20 ° C. for 5 hours in 200 ml of glacial acetic acid and 2 ml of water. The reaction mixture is added to 1.5 L of half-saturated sodium chloride solution with stirring and the separated precipitate is filtered off, washed with water and dried.

4.45 g of 6α-fluoro-prednisolone 17α- (ethyl carbonate) (melting point: 133 to 130 DEG C) are obtained, which are reacted immediately without purification, as follows. The material is dissolved in 60 ml of anhydrous pyridine and the solution is cooled to 0 ° C. before 2.3 ml of propionyl chloride is added. After stirring for 1 hour at 0 ° C. and 1 hour at 20 ° C., the reaction mixture is added to 500 ml of a semi-saturated aqueous sodium chloride solution. The mixture is extracted with methylene chloride and the organic layer is washed with water, dilute hydrochloric acid and water until it is neutral, dried and evaporated to dryness in vacuo. 4.95 g of crude 6-α-fluoro-prednisolone 17α- (ethyl carbonate) -21-propionate obtained at this time was purified as follows.

Ie chromatographed on 250 g silica gel as in Example 2a) and in this case the product was finally recrystallized from ether / petroleum ether to give 2.55 g of 6α-fluoro-prednisolone 17α- (ethyl carbonate) -21-propionate Is obtained (melting point: 147 to 148 ° C)

6α-Fluoro-prednisolone 17α, 21- (diethyl ortho carbonate) used as starting material is prepared as follows according to the method given in German Patent No. 1668079. After addition of 3 ml of tetraethyl ortho carbonate and 0.29 g of P-toluene sulfonic acid, 180 ml of anhydrous dioxane solution containing 4.75 g of 6α-fluoro-prednisolone is stirred at room temperature for 15 hours.

The reaction mixture is added to 950 ml of an aqueous solution containing 1.5 g of sodium bicarbonate, the precipitated crystals are collected, washed with water, dried and recrystallized with acetone.

4.1 g of 6α-fluoro-prednisolone 17α, 21- (diethylortho carbonate) is obtained (melting point: 178 to 180 ° C).

Example 8

6α-fluoro-prednisolone-17α- (ethyl carbonate) -21-chloro acetate

4 g of 6α-fluoro-prednisolone 17α- (ethyl carbonate) are dissolved in 110 ml of anhydrous tetrahydrofuran and 1.69 g of chloroacetic anhydride and 0.65 ml of anhydrous pyridine are added to the solution and the mixture is stirred at room temperature for 28 hours. Let's do it.

20 ml of water are added and the resulting mixture is evaporated to dryness under vacuum at 40 ° C. bath temperature in a rotary evaporator. The residue is dissolved in 150 ml of ethyl acetate and the solution is washed in order of 12 ml of 2W hydrochloric acid, water, sodium bicarbonate solution and water until neutral and the organic layer is dried over sodium sulfate and redevaporated to dryness in vacuo. The residue is recrystallized from diisopropyl ether / petroleum ether.

3.39 g of 6α-fluoro-prednisolone 17α- (ethyl carbonate) -2-chloroacetate are obtained. (Melting point: 134 to 138 ° C)

Example 9

6α-fluoro-prednisolone 17-α- (ethyl carbonate) -21- (morpholinoacetate hydrochloride)

0.5 g of 6α-fluoro-prednisolone 17α- (ethyl carbonate) -21-chloroacetate and 16 ml of acetone solution containing 0.4 ml of morpholine are boiled for 3 hours with reflux. The reaction mixture is evaporated in vacuo, the residue is dissolved in 10 ml of ethyl acetate and the solution is extracted three times with 15.5 ml of 0.10 N hydrochloric acid each time. The combined aqueous layers are made slightly alkaline by adding sodium bicarbonate and a solution. The separated precipitate is collected, washed with a small amount of water and dissolved in ethyl acetate, and then the solution is dried over sodium sulfate and evaporated to dryness in vacuo. The residue is dissolved in 5 ml of absolute ethanol and anhydrous ethanol solution containing 3.2 ml of 0.30N hydrochloric acid is added. The mixture is dried in vacuo and concentrated and the residue is crystallized from hexane.

290 mg of 6α-fluoro-prednisolone 17α- (ethyl carbonate) -21- (morpholino acetate hydrochloride) are obtained (melting point: 185-188 ° C.).

Example 10

6α-methyl-prednisolone 17α- (ethyl carbonate)

21.0 g of 6α-methyl-prednisolone 17α, 21- (diethyl orthocarbonate) is stirred in 700 ml of glacial acetic acid and 1.0 ml of water mixture for 2 hours at room temperature. This mixture is added to 3.0 L of ice water and neutralized with 875 ml of dark ammonia water, and the separated precipitate is filtered and washed with a small amount of water. The combined filtrates are extracted with methylene chloride and the filter residue is dissolved in an organic layer, dried over sodium sulfate and evaporated to dryness in vacuo. Recrystallization from a small amount of methylene chloride and ether yields 16.7 g of 6α-methyl-prednisolone 17α- (ethyl carbonate) (melting point: 188 to 190 ° C.)

6α-Methyl-prednisolone 17α, 21- (diethyl carbonate), used as starting material, is prepared according to German Patent No. 1668079 as follows. After adding 47.0 ml of teraethyl ortho carbonate and 1.05 g of P-luenesulfonic acid, 600 ml of anhydrous dioxane solution containing 17 g of urbason was added and stirred at room temperature for 5 hours, and then the reaction mixture was stirred for 6.0 g of sodium ratio. It is added to 4.0 L of water containing carbonate. The mixture is completed as in Example 7). 21.1 g of 6α-methyl-prednisolone 17α, 21- (diethylcarbonate) are obtained (melting point: 109 to 112 ° C).

Example 11

6α-methyl-prednisolone 17α- (ethyl carbonate) -21- (methyl carbonate)

8.5 g of 6α-methyl-prednisolone 17α- (ethyl carbonate) are dissolved in 85 ml of dioxane anhydride and 42 ml of anhydrous pyridine. 7.2 ml of methyl chloroformate are cooled with ice and added dropwise at 0 ° C. with stirring. After standing at 0 ° C. for 15 hours, the mixture is added with stirring in 800 ml of half-saturated aqueous sodium chloride solution. After standing for 3 hours, the precipitated crystals are collected, washed with water and dried in vacuo at 60 ° C.

Recrystallization with diisopropyl ether / hexane yields 8.2 g of 6α-methyl-prednisolone 17α- (ethylcarbonate) -21- (methyl carbonate) (melting point: 121 to 123 ° C).

Example 12

6α-methyl-prednisolone 17α, 21-bis- (ethyl carbonate)

18 ml of anhydrous dioxane solution containing 2.3 g (= 2 ml) of ethyl chloroformate was added dropwise with ice-cooling stirring to 10.5 ml of anhydrous pyridine ice cold solution containing 3.2 g of 6α-methyl-prednisolone 17α- (enyl carbonate). do. After standing at 0 ° C. for 4.5 hours, the mixture is added with stirring in 200 ml of half-saturated sodium chloride solution.

The reaction mixture was shaken three times with 100 ml of methylene chloride each time and the combined organic layers were washed with 0.5 N hydrochloric acid and water until neutral, dried over sodium sulfate and concentrated to dryness in vacuo. 3.15 g of crude 6α-methyl-prednisolone 17α, 21-bis- (ethyl carbonate) are obtained (melting point: 136 to 140 ° C).

For further purification, the product is fractionated chromatography on a 4x10 cm silica gel column using methylene chloride as eluent. The DAIL fractions obtained by thin layer chromatography are combined and evaporated to dryness in vacuo. Warming with diisopropyl ether yields 2.3 g of 6α-methyl-prednisolone 17α, 21-bis- (ethyl carbonate). (Melting point: 142-143 degreeC).

Example 13

6α-Methyl-Prednisolone-17α- (ethyl carbonate) -21-propionate

0.78 ml of propionyl chloride is added while stirring in 36 ml of pyridine solution containing 3.0 g of 6α-methyl-prednisolone 17α- (ethyl) carbonate while cooling with ice.

The reaction mixture is then stirred at 0 ° C. for 30 minutes and at room temperature for 1 hour and finally added to 200 ml of aqueous sodium chloride solution. Complete as in Example 12).

Chromatography and crystallization with diisopropyl ether yielded 2.4 g of 6α-methyl-prednisolone 17g- (ethylcarbonate) -21-propionate (melting point: 156-158 ° C).

Example 14

6α-methyl-prednisolone 17α- (ethyl carbonate) -21-cyclopropane carboxylate

1.0 ml of cyclo propane carboxylic acid chloride is added to 60 ml of anhydrous pyridine solution containing 5.23 g of 6α-methyl-prednisolone 17α- (ethyl carbonate) with ice-cooling stirring. The reaction mixture is further left at 0 ° C. for 30 minutes at room temperature for 16 hours. After stirring, it is added to 350 ml of water and the reaction mixture is completed as in Example 12 and chromatographed on 180 g of silica gel. Recrystallization with diisopropyl ether / hexane yields 3.93 g of 6α-methyl-prednisolone 17α- (ethyl carbonate) -21-cyclopropane carboxylate (melting point: 167 to 170 ° C).

Example 15

6α-methyl-prednisolone 17α- (ethyl carbonate) -21- (1-adamantoate)

1.73 g of adamantane carboxysilane chloride and 1.0 ml of anhydrous pyridine solution are added to 130 ml of toluene containing 2.0 g of 6α-methyl-prednisolone and heated to the boiling point for 15 hours while refluxing the mixture. The mixture is cooled to room temperature, washed with sodium bicarbonate, washed with water until neutral, dried over sodium sulfate and concentrated to dryness in vacuo.

The residue is chromatographed on to 100 g of silica gel with toluene / ethyl acetate (3: 1) (Comparative Example 12), and when warmed with ether, 1.1 g of 6α-methyl-prednisolone 17α- (ethyl carbonate) -21- ( 1-adamanttoate) is obtained (melting point: 235-266 ° C.).

Example 16

6α-Methyl-Prednisolone 17α- (ethyl carbonate) -21-cyclopentyl-propionate

6.4 g of cyclopentylpropionyl chloride was added dropwise over 30 minutes in a 30 ° C. solution of 23 ml anhydrous pyridine and 25 ml anhydrous acetone containing 5.0 g of 6α-methyl-prednisolone 17α- (ethyl carbonate) with stirring under nitrogen gas. do. The mixture is stirred for further 1 hour at 46-48 ° C. 2.17 ml of diethylamino ethanol is added dropwise to this temperature over 5 minutes, the mixture is stirred for 20 more minutes, cooled to 20 ° C. and 30 ml of water is added over 20 minutes. Further stirring for 20 minutes to evaporate the organic solvent in vacuo and chromatography the residue obtained as in Example 12 to give 2.6 g of 6α-methyl-prednisolone 17α- (ethyl carbonate) -21-cyclopentylpropionate. (Melting point: 175 to 176 ° C).

Example 17

a) 1 g of prednisolone 17- (methyl carbonate) in place of methylchloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of iso-butyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) 1.3 ml of cyclopentyl propionyl chloride were reacted as in Example 4a) and the product was completed to

1) prednisolone 17- (methyl carbonate) -21- (methyl carbonate),

2) prednisolone 17- (methyl carbonate) -21- (ethyl carbonate),

3) prednisolone 17- (methyl carbonate) -21 (n-propyl carbonate),

4) prednisolone 17- (methyl carbonate) -21- (n-butyl carbonate),

5) prednisolone 17- (methyl carbonate) -21- (isopropyl carbonate),

6) prednisolone 17- (methyl carbonate) -21- (isobutyl carbonate),

7) prednisolone 17- (methyl carbonate) -21-acetate,

8) prednisolone 17- (methyl carbonate) -21-propionate,

9) prednisolone 17- (methyl carbonate) -21-butarate,

10) prednisolone 17- (methyl carbonate) -21-valorate,

11) prednisolone 17- (methyl carbonate) -21-cyclopropanecarboxylate,

12) Prednisolone 17- (methyl carbonate) -21-cyclopentylpropionate is obtained respectively.

b) Reacting 3 g of prednisolone 17- (methyl carbonate) with methanesulfonyl chloride as in Example 2f) and completing the product to crystallize with ether yields prednisolone 17- (methyl carbonate) -21-methane sulfonate .

Use of equimolar amounts of P-toluenesulfonylchloride or P-chlorobenzenesulfonyl chloride instead of methane sulfonyl chloride provides the corresponding prednisolone 17- (methyl carbonate) -21-P-toluene sulfonate, prednisolone 17- (methyl carbonate) -21-P-chloro benzenesulfonate is obtained respectively.

c) The prednisolone dimethyl orthocarbonate (Rf = 0.6) required for the first time in the reaction is prepared from prednisolone and tetramethyl ortho-carbonate according to German Patent No. 1668079.

0.4)를 얻는다.The first mentioned compound was then hydrolyzed as in Example 1c) to prednisolone 17- (methyl carbonate) (Rf

0.4).

Example 18

a) 1 g of prednisolone 17- (methyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) React with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete the product to yield the corresponding

1) prednisolone 17- (methyl carbonate) -21- (methyl carbonate),

2) prednisolone 17- (methyl carbonate) -21- (ethyl carbonate),

3) prednisolone 17- (methyl carbonate) -21- (n-propyl carbonate),

4) prednisolone 17- (methyl carbonate) -21- (n-butyl carbonate),

5) prednisolone 17- (methyl carbonate) -21- (isopropyl carbonate),

6) prednisolone 17- (methyl carbonate) -21- (isobutyl carbonate),

7) prednisolone 17- (methyl carbonate) -21-acetate,

8) prednisolone 17- (methyl carbonate) -21-propionate,

9) prednisolone 17- (methyl carbonate) -21-butyrate,

10) prednisolone 17- (methyl carbonate) -21-valorate,

11) prednisolone 17- (methyl carbonate) -21-cyclopropane carboxylate.

12) Prednisolone 17- (methyl carbonate) -21-cyclopentylpropionate is obtained respectively.

b) Reacting 3 g of prednisolone 17- (methyl carbonate) with methanesulfonyl chloride as in example 2f) and completing the product to crystallize with ether gives Obtained.

If equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride are used instead of methane sulfonyl chloride, the corresponding prednisolone 17- (methyl carbonate) 21-P-toluene sulfonate or prednisolone 17- (methyl carbonate)- 21-P-chlorobenzene sulfonate is obtained respectively.

c) Prednisolone dimethylortho carbonate (Rf = 0.6), initially required for the reaction, is prepared from prednisolone and tetramethyl orthocarbonate in accordance with Federal Patent No. 1668079.

0.4)를 얻는다.The compound mentioned initially was then hydrolyzed as in Example 1c) to prednisolone 17- (methyl carbonate) (Rf

0.4).

Example 19

a) 1 g of cortisone 17- (methyl carbonate) in place of methylchloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) 1.3 ml of cyclopentyl chloride were reacted as in Example 4a) and the product was completed to in each case correspond to

1) Cortisone 17- (methyl carbonate) -21- (methyl carbonate),

2) cortisone 17- (methyl carbonate) -21- (ethyl carbonate),

3) cortisone 17- (methyl carbonate) -21- (n-propyl carbonate),

4) cortisone 17- (methyl carbonate) -21- (n-butyl carbonate),

5) cortisone 17- (methyl carbonate) -21- (isopropyl carbonate),

6) cortisone 17- (methyl carbonate) -21- (isobutyl carbonate),

7) cortisone 17- (methyl carbonate) -21-acetate,

8) cortisone 17- (methyl carbonate) -21-propionate,

9) cortisone 17- (methyl carbonate) -21-butyrate,

10) cortisone 17- (methyl carbonate) -21-valorate,

11) Cortisone 17- (methyl carbonate) -21-cyclopropane carboxylate

12) Cortisone 17- (methyl carbonate) -21-cyclopentylpropionate is obtained.

b) 3 g of Cortisone 17- (methyl carbonate) was reacted with methanesulfonylchloride as in Example 2f) and the product was completed and crystallized with ether to give Cortisone 17- (methylcarbonate) -21-methane-sulfonate Lose.

If equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzene sulfonyl chloride are used instead of methane sulfonyl chloride, the corresponding cortisone 17- (methyl carbonate) 21-P-toluenesulfonate, cortisone 17- (methyl carbonate)- 21-P-chlorobenzenesulfonate is obtained.

c) Cortisone dimethylortho carbonate (Rf = 0.6), initially required for the reaction, is prepared from cortisone and tetramethylortho carbonate in accordance with Federal Patent No. 1668079.

0.4)를 얻는다.Subsequently, the first mentioned compound was hydrolyzed as in Example 1c) to form Cortisone 17- (methyl carbonate) (Rf

0.4).

Example 20

a) 1 g cortisone 17- (methyl carbonate). Instead of methylchloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) 1.3 ml of cyclopentyl propionyl chloride was reacted as in Example 4a) and the product was completed to in each case correspond to

1) Cortisol 17- (methyl carbonate) -21- (methyl carbonate),

2) cortisol 17- (methyl carbonate) -21- (ethyl carbonate),

3) cortisol 17- (methyl carbonate) -21- (n-propyl carbonate),

4) cortisol 17- (methyl carbonate) -21- (n-butyl carbonate),

5) Cortisol 17- (methyl carbonate) -21- (isopropyl carbonate),

6) cortisol 17- (methyl carbonate) -21- (isobutyl carbonate),

7) cortisol 17- (methyl carbonate) -21-acetate,

8) cortisol 17- (methyl carbonate) -21-propionate,

9) cortisol 17- (methyl carbonate) -21-butyrate,

10) cortisol 17- (methyl carbonate) -21-valorate,

11) Cortisol 17- (methyl carbonate) -21-cyclopropanecarboxylic acid.

12) Cortisol 17- (methyl carbonate) -21-cyclopentyl propio and nate are obtained.

b) 3 g of Cortisol 17- (methyl carbonate) is reacted with methanesulfonyl chloride as in Example 2f) and the product is completed and crystallized with ether to give Cortisol 17- (methyl carbonate) -21-methane-sulfonate Obtained.

If equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride are used instead of methanesulfonyl chloride, the corresponding cortisol 17- (methyl carbonate) 21-P-toluene sulfonate or cortisol 17- (methyl carbonate)- 21-P-chlorobenzenesulfonate is obtained.

0.6)는 독일연방공화국 특허 제1668079호에 따라 코르티솔 및 테트라메틸 오르토카보네이트로 부터 제조한다.c) Cortisol dimethyl orthocarbonate (Rf first required for the reaction)

0.6) are prepared from cortisol and tetramethyl orthocarbonate according to Federal Republic of Germany Patent No. 1668079.

0.4)를 얻는다.The compound mentioned initially was then hydrolyzed as in Example 1c) to form Cortisol 17- (methyl carbonate) (Rf

0.4).

Example 21

a) 1 g of beclomethasone 17- (methyl carbonate) in place of methylchloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropylchloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) React with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete the product to in each case correspond to

1) beclomethasone 17- (methyl carbonate) -21- (methyl carbonate),

2) beclomethasone 17- (methyl carbonate) -21- (ethyl carbonate),

3) beclomethasone 17- (methyl carbonate) -21- (n-propyl carbonate),

4) beclomethasone 17- (methyl carbonate) -21- (n-butyl carbonate),

5) beclomethasone 17- (methyl carbonate) -21- (isopropylcarbonate),

6) beclomethasone 17- (methyl carbonate) -21- (isobutyl carbonate),

7) beclomethasone 17- (methyl carbonate) -21-acetate,

8) beclomethasone 17- (methyl carbonate) -21-propionate,

9) beclomethasone 17- (methyl carbonate) -21-butyrate,

10) beclomethasone 17- (methyl carbonate) -21-valorate,

11) beclomethasone 17- (methyl carbonate) -21-cyclopropane carboxylate,

12) Beclomethasone 17- (methyl carbonate) -21-cyclopentylpropionate is obtained.

b) 3 g of beclomethasone 17- (methyl carbonate) is reacted with methanesulfonyl chloride as in Example 2f) and the product is completed and crystallized with ether to give beclomethasone 17- (methyl carbonate) -21- Methanesulfonate is obtained.

Use of equimolar amounts of -P-toluene sulfonyl chloride, or P-chlorobenzenesulfonyl chloride instead of methane sulfonyl chloride, results in the corresponding beclomethasone 17- (methyl carbonate) -21-P-toluene sulfonate or bechro Metason 17- (methyl carbonate) -21-P-chlorobenzenesulfonate is obtained.

c) The first required beclomethasone dimethyl orthocarbonate (R = 0.6) in the reaction is prepared from beclomethasone and tetramethyl orthocarbonate in accordance with German Patent No. 1668079.

The initially mentioned compound is then hydrolyzed as in Example 1c) to afford beclomethasone 17- (methyl carbonate) (Rf-0.4).

Example 22

a) 1 g of 6α-fluorodexamethasone 17- (methyl carbonate) in place of cyclopentylpropionyl chloride

1) 0.8 ml methyl chloroformate,

2) 0.80 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) React with 1.3 ml of cyclopentylpropionyl chloride as in Example 4a) and complete the product, in each case the corresponding

1) 6α-fluorodexamethasone 17- (methyl carbonate) -21- (methylcarbonate),

2) 6α-fluorodexamethasone 17- (methyl carbonate) -21- (ethylcarbonate),

3) 6α-fluorodexamethasone 17- (methyl carbonate) -21- (n-propyl carbonate),

4) 6α-fluorodexamethasone 17- (methyl carbonate) -21- (n-butyl carbonate),

5) 6α-fluoro dexamethasone 17- (methyl carbonate) -21- (isopropyl carbonate),

6) 6α-fluorodexamethasone 17- (methyl carbonate) -21- (isobutyl carbonate),

7) 6α-fluorodexamethasone 17- (methyl carbonate) -21-acetate,

8) 6α-fluorodexamethasone 17- (methyl carbonate) -21-propionate,

9) 6α-fluorodexamethasone 17- (methyl carbonate) -21-butyrate,

10) 6α-fluorodexamethasone 17- (methyl carbonate) -21-valorate,

11) 6α-fluorodexamethasone 17- (methyl carbonate) -21-cyclopropane carboxylate.

12) 6α-fluorodexamethasone 17- (methyl carbonate) -21-cyclopentylpropionate is obtained, respectively.

b) 3 g of 6α-fluorodexxamethasone 17- (methylcarbonate) is reacted with methanesulfonyl chloride as in Example 2f) and the product is completed and crystallized with ether to give 6α-fluorodexamemethasone 17- (methyl carbonate)- 21-methane sulfonate is obtained.

If P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride is used instead of methane sulfonyl chloride, the corresponding 6α-fluorodexamemethasone 17- (methyl carbonate) -21-P-toluene sulfonate, 6α-fluorodexamethason 17 -(Methyl carbonate) -21-P-chlorobenzene sulfonate is obtained.

c) The 6α-fluorodexamethasone dimethyl ortho carbonate (Rf-0.6) initially required for the reaction is prepared from 6α-fluorodexamemethasone and tetramethylortho carbonate in accordance with Federal Patent No. 1668079.

The compound mentioned initially is then hydrolyzed as in Example 1c) to afford 6α-fluorodexamemethasone 17- (methyl carbonate) (Rf-0.4).

Example 23

a) 1 g of betamethasone 17- (methyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) React with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete the product to in each case correspond to

1) betamethasone 17- (methyl carbonate) -21- (methyl carbonate),

2) betamethasone 17- (methyl carbonate) -21- (ethyl carbonate),

3) betamethasone 17- (methyl carbonate) -21- (n-propyl carbonate),

4) betamethasone 17- (methyl carbonate) -21- (n-butyl carbonate),

5) betamethasone 17- (methyl carbonate) -21- (isopropyl carbonate),

6) betamethasone 17- (methyl carbonate) -21- (isobutyl carbonate),

7) betamethasone 17- (methyl carbonate) -21-propionate,

9) betamethasone 17- (methyl carbonate) -21-butyrate,

10) betamethasone 17- (methyl carbonate) -21-valorate,

11) Betamethasone 17- (methyl carbonate) -21-cyclopropane carboxylate.

12) Betamethasone 17- (methyl carbonate) -21-cyclopentylpropionate is obtained.

b) 3 g of betamethasone 17- (methyl carbonate) was reacted with methanesulfonyl chloride as in Example 2f) and the product was completed and crystallized with ether to give betamethasone 17- (methylcarbonate) -21-methanesulfonate Lose.

Reaction with an equimolar amount of P-toluene sulfonylchloride or P-chlorobenzenesulfonyl chloride instead of methane sulfonyl chloride results in the corresponding betamethasone 17- (methyl carbonate) -21-P-toluene sulfonate betamethasone 17- (methyl carbonate)- 21-P-chloro benzenesulfonate is obtained.

0.4)를 얻는다.c) Betamethasone dimethylorthocarbonate (Rf = 0.6), initially required for the reaction, is prepared from betamethasone and tetramethyl orthocarbonate according to Federal Republic of Patent No. 1668079. Subsequently, the first mentioned compound was hydrolyzed as in Example 1c) to betamethasone 17- (methyl carbonate) (Rf

0.4).

Example 24

a) 1 g of 6α-fluoro-prednisolone 17-1) methyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) React with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete the product to in each case correspond to

1) 6α-fluoro-prednisolone 17- (methyl carbonate) -21- (methyl carbonate),

2) 6α-fluoro-prednisolone 17- (methyl carbonate) -21- (ethyl carbonate),

3) 6α-fluoro-prednisolone 17- (methyl carbonate) -21- (n-propyl carbonate),

4) 6α-fluoro-prednisolone 17- (methyl carbonate) -21- (n-butyl carbonate),

5) 6α-fluoro-prednisolone 17- (methyl carbonate) -21- (isopropyl carbonate),

6) 6α-fluoro-prednisolone 17- (methyl carbonate) -21- (isobutyl carbonate),

7) 6α-fluoro-prednisolone 17- (methyl carbonate) -21-acetate,

8) 6α-fluoro-prednisolone 17- (methyl carbonate) -21-propionate,

9) 6α-fluoro-prednisolone 17- (methyl carbonate) -21-butyrate,

10) 6α-fluoro-prednisolone 17- (methyl carbonate) -21-valorate,

11) 6α-fluoro-prednisolone 17- (methyl carbonate) -21-cyclopropane carboxylate and

12) 6α-fluoro-prednisolone 17- (methyl carbonate) -21-cyclopentylpropionate is obtained.

b) 3 g of 6α-fluoro-prednisolone 17- (methyl carbonate) is reacted with methanesulfonyl chloride as in Example 2f) and the product is completed and crystallized with ether to give 6α-fluoro-prednisolone 17- (methyl carbonate ) -21-methanesulfonate is obtained.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methanesulfonyl chloride results in the corresponding 6α-fluoro-prednisolone 17- (methyl carbonate) -21-P-toluenesulfonate, 6α- Fluoroprednisolone 17- (methyl carbonate) -21-P-chlorobenzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1668079호에 제시된 바에 따라 6α-플루오로-프레드니솔론 및 테트라메틸 오르토카보네이트로부터 제조한다.c) 6α-fluoro-prednisolone dimethyl orthocarbonate (Rf initially required for the reaction)

0.6) is prepared from 6α-fluoro-prednisolone and tetramethyl orthocarbonate as set forth in Federal Republic of Patent No. 1668079.

0.4)를 얻는다.The initially mentioned compound was then hydrolyzed as in Example 1c) to give 6α-fluoro-prednisolone 17- (methyl carbonate) (Rf

0.4).

Example 25

a) 1 g of 16α- or β-methyl prednisolone 17- (methyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) React with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete the product to in each case correspond to

1) 16α- or β-methyl prednisolone 17- (methyl carbonate) -21- (methyl carbonate),

2) 16α- or β-methyl prednisolone 17- (methyl carbonate) -21- (ethyl carbonate),

3) 16α- or β-methyl prednisolone 17- (methyl carbonate) -21- (n-propyl carbonate),

4) 16α or β-methyl prednisolone 17- (methyl carbonate) -21- (n-butyl carbonate),

5) 16α- or β-methyl prednisolone 17- (methyl carbonate) -21- (isopropyl carbonate),

6) 16α- or β-methyl prednisolone 17- (methyl carbonate) -21- (isobutyl carbonate),

7) 16α- or β-methyl prednisolone 17- (methyl carbonate) -21-acetate,

8) 16α- or β-methyl prednisolone 17- (methyl carbonate) -21-propionate,

9) 16α- or β-methyl prednisolone 17- (methyl carbonate) -21-butyrate,

10) 16α- or β-methyl prednisolone 17- (methyl carbonate) -21-valorate,

11) 16α- or β-methyl prednisolone 17- (methyl carbonate) -21-cyclopropane carboxylate.

12) 16α- or β-methyl prednisolone 17- (methyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 16α- or β-methyl prednisolone 17- (methyl carbonate) was reacted as in Example 2f) and the product was completed and crystallized with ether to give 16α- or β-methyl prednisolone 17- (methyl carbonate) -21 Methane sulfonate is obtained.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methane sulfonyl chloride results in the corresponding 16α- or β-methyl prednisolone 17- (methyl carbonate) -21-P-toluene sulfonate, or 16α- or β-methyl prednisolone 17- (methyl carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)는 독일연방공화국 특허 제1668079호에 따라 16α-또는 β-메틸 프레드니솔론 및 테트라메틸 오르토 카보네이트로 부터 제조한다.c) 16α, or β-methyl prednisolone dimethyl ortho carbonate (Rf, initially required in the reaction)

0.6) is prepared from 16α- or β-methyl prednisolone and tetramethyl ortho carbonate according to German Patent No. 1668079.

0.4)를 얻는다.The first mentioned compound was then hydrolyzed as in Example 1c) to give 16α or β-methyl prednisolone 17- (methyl carbonate) (Rf

0.4).

Example 26

a) 1 g of 6α, 16α- or β-dimethyl-prednisolone 17- (methyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) React with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete the product to in each case correspond to

1) 6α, 16α- or β-dimethyl-prednisolone 17- (methyl carbonate) -21- (methyl carbonate),

2) 6α, 16α- or β-dimethyl-prednisolone 17- (methyl carbonate) -21- (ethyl carbonate),

3) 6α, 16α- or β-dimethyl-prednisolone 17- (methyl carbonate) -21- (n-propyl carbonate),

4) 6α, 16α- or β-dimethyl-prednisolone 17- (methyl carbonate) -21- (n-butyl carbonate),

5) 6α, 16α- or β-dimethyl-prednisolone 17- (methyl carbonate) -21- (isopropyl carbonate),

6) 6α, 16α- or β-dimethyl-prednisolone 17- (methyl carbonate) -21- (isobutyl carbonate),

7) 6α, 16α- or β-dimethyl-prednisolone 17- (methyl carbonate) -21-acetate,

8) 6α, 16α- or β-dimethyl-prednisolone 17- (methyl carbonate) -21-propionate,

9) 6α, 16α- or β-dimethyl-prednisolone 17- (methyl carbonate) -21-butyrate,

10) 6α, 16α- or β-dimethyl-prednisolone 17- (methyl carbonate) -21-valorate,

11) 6α, 16α- or β-dimethyl-prednisolone 17- (methyl carbonate) -21-cyclopropane carboxylate.

12) 6α, 16α- or β-dimethyl-prednisolone 17- (methyl carbonate) -21-cyclopentylpropionate is obtained.

b) 3 g of 6α, 16α- or β-dimethyl-prednisolone 17- (methyl carbonate) is reacted with methanesulfonyl chloride as in Example 2f) and the product is crystallized with ether to give 6α, 16α- or β- Dimethyl-prednisolone 17- (methyl carbonate) -21-methane sulfonate is obtained.

Reaction with an equimolar amount of P-toluene sulfonyl chloride or P-chlorobenzene sulfonyl chloride instead of methane sulfonyl chloride results in the corresponding 6α, 16α- or β-dimethyl-prednisolone 17- (methyl carbonate) -21-P-toluene sulfo Nate, 6α, 16α- or β-dimethyl-prednisolone 17- (methyl carbonate) -21-P-chlorobenzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1668079호에 따라 6α,16α-또는 β-디메틸-프레드니솔론 및 테트라메틸 오르토 카보네이트로부터 제조한다.c) 6α, 16α- or β-dimethyl-prednisolone dimethyl ortho carbonate (Rf first required in the reaction)

0.6) is prepared from 6α, 16α- or β-dimethyl-prednisolone and tetramethyl ortho carbonate in accordance with Federal Patent No. 1668079.

0.4)를 얻는다.The initially mentioned compound was then hydrolyzed as in Example 1c) to give 6α, 16α- or β-dimethyl-prednisolone 17- (methyl carbonate) (Rf

0.4).

Example 27

a) 1 g of 9α-chloro-16α-methyl-prednisolone-17- (methyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) React with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete the product.

1) 9α-chloro-16α-methyl-prednisolone 17- (methyl carbonate) -21- (methyl carbonate),

2) 9α-chloro-16α-methyl-prednisolone 17- (methyl carbonate) -21- (ethyl carbonate),

3) 9α-chloro-16α-methyl-prednisolone 17- (methyl carbonate) -21- (n-propyl carbonate),

4) 9α-chloro-16α-methyl-prednisolone 17- (methyl carbonate) -21- (n-butyl carbonate),

5) 9α-chloro-16α-methyl-prednisolone 17- (methyl carbonate) -21- (isopropyl carbonate),

6) 9α-chloro-16α-methyl-prednisolone 17- (methyl carbonate) -21- (isobutyl carbonate),

7) 9α-chloro-16α-methyl-prednisolone 17- (methyl carbonate) -21-acetate,

8) 9α-chloro-16α-methyl-prednisolone 17- (methyl carbonate) -21-propionate,

9) 9α-chloro-16α-methyl-prednisolone 17- (methyl butyrate) -21-butyrate,

10) 9α-chloro-16α-methyl-prednisolone 17- (methyl carbonate) -21-valorate,

11) 9α-chloro-16α-methyl-prednisolone 17- (methyl carbonate) -21-cyclopropane carboxylate.

12) 9α-chloro-16α-methyl-prednisolone 17- (methyl carbonate) -21-cyclopentyl propionate is obtained respectively.

b) 3 g of 9α-chloro-16α-methyl-prednisolone 17- (methyl carbonate) was reacted with methanesulfonyl chloride as in Example 2f) and the product was completed and crystallized with ether to give 9α-chloro-16α-methyl- Prednisolone 17- (methyl carbonate) -21-methane sulfonate is obtained.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methane sulfonyl chloride provides the corresponding 9α-chloro-methyl-prednisolone 17- (methyl carbonate) 21-P-toluene sulfonate, 9α- Chloro-16α-methyl-prednisolone 17- (methyl carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)는 독일연방공화국 특허 제1668079호에 따라 9α-클로로-16α-메틸-프레드니솔론 및 테트라메틸 오르토 카보네이트로부터 제조한다.c) 9α-chloro-16α-methyl prednisolone dimethyl ortho carbonate (Rf initially required for the reaction)

0.6) is prepared from 9α-chloro-16α-methyl-prednisolone and tetramethyl ortho carbonate according to Federal Republic of Patent No. 1668079.

0.4)를 얻는다.Subsequently, the first mentioned compound was hydrolyzed as in Example 1c) to give 9α-chloro-16α-methyl-prednisolone 17- (methyl carbonate) (Rf

0.4).

Example 28

a) 1 g of 9α-chloro-prednisolone 17- (methyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) React with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete the product to in each case correspond to

1) 9α-chloro-prednisolone 17- (methyl carbonate) -21- (methyl carbonate),

2) 9α-chloro-prednisolone 17- (methyl carbonate) -21- (ethyl carbonate),

3) 9α-chloro prednisolone 17- (methyl carbonate) -21- (n-propyl carbonate),

4) 9α-chloro-prednisolone 17- (methyl carbonate) -21- (n-butyl carbonate),

5) 9α-chloro-prednisolone 17- (methyl carbonate) -21- (isopropyl carbonate),

6) 9α-chloro-prednisolone 17- (methyl carbonate) -21- (isobutyl carbonate),

7) 9α-chloro-prednisolone 17- (methyl carbonate) -21-acetate,

8) 9α-chloro-prednisolone 17- (methyl carbonate) -21-propionate,

9) 9α-chloro-prednisolone 17- (methyl carbonate) -21-butyrate,

10) 9α-chloro-prednisolone 17- (methyl carbonate) -21-valorate,

11) 9α-chloro-prednisolone 17- (methyl carbonate) -21-cyclopropane carboxylate,

12) 9α-chloro-prednisolone 17- (methyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 9α-chloro-prednisolone 17- (methyl carbonate) was reacted with methane sulfonyl chloride as in Example 2f) and the product was completed and crystallized with ether to give 9α-chloro-prednisolone 17- (methyl carbonate)- 21-methane sulfonate is obtained.

If equimolar amounts of P-toluene sulfonyl chloride or P-chlorosulfonyl chloride are used instead of methane sulfonyl chloride, the corresponding 9α-chloro-prednisolone 17- (methyl carbonate) -21-P-toluene sulfonate or 9α-chloro- Prednisolone 17- (methyl carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)는 독일연방공화국 특허 제1668079호에 따라 9α-클로로-프레드니솔론 및 테트라 메틸 오르토 카보네이트로 부터 제조한다.c) 9α-chloro-prednisolone dimethyl ortho carbonate (Rf initially required for the reaction)

0.6) is prepared from 9α-chloro-prednisolone and tetra methyl ortho carbonate in accordance with Federal Patent No. 1668079.

0.4)를 얻는다.Subsequently, the initially mentioned compound was hydrolyzed as in Example 1c) to give 9α-chloro-prednisolone 17- (methyl carbonate) (Rf

0.4).

Example 29

a) 1 g of prednisolone 17- (ethyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloromate,

7) 0.9 ml of butyryl chloride,

8) 1 ml of valeryl chloride,

9) 1 ml of cyclopropane carboxylic acid chloride and

10) Reaction with 1.3 ml of cyclopentyl propionyl chloride in the manner described in Example 4a) to complete the product.

In each case

1) prednisolone 17- (ethyl carbonate) -21- (methyl carbonate),

2) prednisolone 17- (ethyl carbonate) -21- (ethyl carbonate),

3) prednisolone 17- (ethyl carbonate) -21- (n-propyl carbonate),

4) prednisolone 17- (ethyl carbonate) -21- (n-butyl carbonate),

5) prednisolone 17- (ethyl carbonate) -21- (isopropyl carbonate),

6) prednisolone 17- (ethyl carbonate) -21- (isobutyl carbonate),

7) prednisolone 17- (ethyl carbonate) -21-butyrate,

8) prednisolone 17- (ethyl carbonate) -21-valorate,

9) prednisolone 17- (ethyl carbonate) -21-cyclopropane carboxylate and

10) Prednisolone 17- (ethyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of prednisolone 17- (ethyl carbonate) are reacted with methanesulfonyl chloride in the manner described in Example 2f) to complete the product. After crystallization with ether, prednisolone 17- (ethyl carbonate) -21-methanesulfonate is obtained.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzene sulfonyl chloride in place of methane sulfonyl chloride results in the corresponding prednisolone 17- (ethyl carbonate) -21-P-toluene sulfonate or prednisolone 17- (ethyl carbonate ) -21-P-chlorobenzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1668079호에 따라서 프레드니솔론 및 테트라에틸 오르토 카보네이트로부터 제조한다. 계속해서, 전술한 화합물은 실시예 1c)에 기술된 방법에 의해 프레드니솔론 17-(에틸 카보네이트)(Rf

0.4)로 가수분해된다.c) prednisolone diethyl ortho carbonate (Rf first required for the reaction)

0.6) is prepared from prednisolone and tetraethyl ortho carbonate in accordance with Federal Patent No. 1668079. Subsequently, the above-mentioned compound was prepared by prednisolone 17- (ethyl carbonate) (Rf) by the method described in Example 1c).

0.4).

Example 30

a) 1 g of prednisolone 17- (ethyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) The reaction is completed with 1.3 ml of cyclopentyl propionyl chloride by the method described in Example 4a) to complete the product.

In each case

1) prednisolone 17- (ethyl carbonate) -21- (methyl carbonate),

2) prednisolone 17- (ethyl carbonate) -21- (ethyl carbonate),

3) prednisolone 17- (ethyl carbonate) -21- (propyl carbonate),

4) prednisolone 17- (ethyl carbonate) -21- (n-butyl carbonate),

5) prednisolone 17- (ethyl carbonate) -21- (isopropyl carbonate),

6) prednisolone 17- (ethyl carbonate) -21- (isobutyl carbonate),

7) prednisolone 17- (ethyl carbonate) -21-acetate,

8) prednisolone 17- (ethyl carbonate) -21-propionate,

9) prednisolone 17- (ethyl carbonate) -21-propionate,

10) prednisolone 17- (ethyl carbonate) -21-valorate,

11) prednisolone 17- (ethyl carbonate) -21-cyclopropane carbonate and

12) Prednisolone 17- (ethyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of prednisolone 17- (ethyl carbonate) are reacted with methane sulfonyl chloride by the method described in Example 2f) to complete the product. Crystallization with ether gives prednisolone 17- (ethyl carbonate) -21-methanesulfonate.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzene sulfonyl chloride instead of methanesulfonyl chloride results in the corresponding prednisolone 17- (ethyl carbonate) -21-P-toluene sulfonate or prednisolone 17- (ethyl carbonate ) -21-P-chlorobenzenesulfonate is obtained.

0.6)는 독일연방공화국 특허 제1668079호에 따라 프레드니솔론 및 테트라에틸 오르토 카보네이트로부터 제조한다. 계속해서 전술한 화합물을 실시예 1c)에 기술된 방법으로 프레드니솔론 17-(에틸 카보네이트)(Rf

0.4)로 가수분해시킨다.c) Prednisolone diethyl ortho carbonate (Rf required for the first time in the reaction)

0.6) are prepared from prednisolone and tetraethyl ortho carbonate according to Federal Republic of Germany Patent No. 1668079. Subsequently, the aforementioned compound was prepared in the manner described in Example 1c) by prednisolone 17- (ethyl carbonate) (Rf

0.4).

Example 31

a) 1 g cortisol 17- (ethyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.9 ml of butyryl chloride,

9) 1 ml of valeryl chloride,

10) 1 ml of cyclopropane carboxylic acid chloride and

11) Reaction with 1.3 ml of cyclopentyl propionyl chloride in the manner described in Example 4a) to complete the product.

In each case

1) Cortisol 17- (ethyl carbonate) -21- (methyl carbonate),

2) cortisol 17- (ethyl carbonate) -21- (ethyl carbonate),

3) cortisol 17- (ethyl carbonate) -21- (n-propyl carbonate),

4) cortisol 17- (ethyl carbonate) -21- (n-propyl carbonate),

5) Cortisol 17- (ethyl carbonate) -21- (isopropyl carbonate),

6) cortisol 17- (ethyl carbonate) -21- (isobutyl carbonate),

7) cortisol 17- (ethyl carbonate) -21-acetate,

8) cortisol 17- (ethyl carbonate) -21-butyrate,

9) cortisol 17- (ethyl carbonate) -21-valorate,

10) Cortisol 17- (ethyl carbonate) -21-cyclopropane carboxylate and

11) Cortisol 17- (ethyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of Cortisol 17- (ethyl carbonate) is reacted with methane sulfonyl chloride by the method described in Example 2f) and the product is completed. Cortisol 17- (ethyl carbonate) -21-methane sulfonate is obtained after crystallization from ether.

Use of equimolar amounts of P-toluenesulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methane sulfonyl chloride results in the corresponding cortisol 17- (ethyl carbonate) -21-P-toluenesulfonate or cortisol 17- (ethyl carbonate ) -21-P-chlorobenzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1668079호에 따라서 코르티솔 및 테트라에틸 오르토 카보네이트로부터 제조한다.c) Cortisol diethyl ortho carbonate (Rf first required for the reaction)

0.6) is prepared from cortisol and tetraethyl ortho carbonate in accordance with Federal Patent No. 1668079.

0.4)로 가수분해 시킨다.Subsequently, the aforementioned compound was added to Cortisol 17- (ethyl carbonate) (Rf) according to the method described in Example 1c).

0.4) to hydrolysis.

Example 32

a) 1 g of beclomethasone 17- (ethyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) React with 1.3 ml of cyclopentyl propionyl chloride by the method described in Example 4a) to complete the product.

In each case

1) beclomethasone 17- (ethyl carbonate) -21- (methyl carbonate),

2) beclomethasone 17- (ethyl carbonate) -21- (ethyl carbonate),

3) beclomethasone 17- (ethyl carbonate) -21- (n-propyl carbonate),

4) beclomethasone 17- (ethyl carbonate) -21- (n-butyl carbonate),

5) beclomethasone 17- (ethyl carbonate) -21- (isopropyl carbonate),

6) beclomethasone 17- (ethyl carbonate) -21- (isobutyl carbonate),

7) beclomethasone 17- (ethyl carbonate) -21-acetate,

8) beclomethasone 17- (ethyl carbonate) -21-propionate,

9) beclomethasone 17- (ethyl carbonate) -21-butyrate,

10) beclomethasone 17- (ethyl carbonate) -21-valorate,

11) beclomethasone 17- (ethyl carbonate) -21-cyclopropane carboxylate and

12) Beclomethasone 17- (ethyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of beclomethasone 17- (ethyl carbonate) are reacted with methanesulfonyl chloride in the manner described in Example 2f) to complete the product. After crystallization from ether, beclomethasone 17- (ethyl carbonate) -21-methanesulfonate is obtained.

If equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzene sulfonyl chloride are used in place of methane sulfonyl chloride, beclomethasone 17- (ethyl carbonate) -21-P-toluene sulfonate or becromethasone 17 -(Ethyl carbonate) -21-P-chloro benzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1668079호에 따라서 베크로 메타손 및 테트라에틸 오르토 카보네이트로 부터 제조된다. 계속해서 전술한 화합물을 실시예 1c)에 기술된 방법으로 베크로메타손 17-(에틸 카보네이트)(Rf

0.4)로 가수분해시킨다.c) the first required beclomethasone diethyl ortho carbonate (Rf)

0.6) is prepared from Beckro metason and tetraethyl ortho carbonate in accordance with Federal Patent No. 1668079. Subsequently, the aforementioned compound was added to beclomethasone 17- (ethyl carbonate) (Rf by the method described in Example 1c).

0.4).

Example 33

a) 1 g of 6α-fluoro dexamethasone 17- (ethyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) The product is reacted with 1.3 ml of cyclopentyl propionyl chloride by the method described in Example 4a).

In each case

1) 6α-fluoro dexamethasone 17- (ethyl carbonate) -21- (methyl carbonate),

2) 6α-fluoro dexamethasone 17- (ethyl carbonate) -21- (ethyl carbonate),

3) 6α-fluoro dexamethasone 17- (ethyl carbonate) -21- (n-propyl carbonate),

4) 6α-fluoro dexamethasone 17- (ethyl carbonate) -21- (n-butyl carbonate),

5) 6α-fluoro dexamethasone 17- (ethyl carbonate) -21- (isopropyl carbonate),

6) 6α-fluoro dexamethasone 17- (ethyl carbonate) -21- (isobutyl carbonate),

7) 6α-fluoro dexamethasone 17- (ethyl carbonate) -21-acetate,

8) 6α-fluoro dexamethasone 17- (ethyl carbonate) -21-propionate,

9) 6α-fluoro dexamethasone 17- (ethyl carbonate) -21-butyrate,

10) 6α-fluoro dexamethasone 17- (ethyl carbonate) -21-valorate,

11) 6α-fluoro dexamethasone 17- (ethyl carbonate) -21-cyclopropane carboxylate and

12) Obtain 6α-fluoro dexamethasone 17- (ethyl carbonate) -21-cyclopentyl propionate.

b) 3 g of 6α-fluoro dexamethasone 17- (ethyl carbonate) are reacted with methanesulfonyl chloride in the manner described in Example 5f) to complete the product. Crystallization from ether gives 6α-fluoro dexamethasone 17- (ethyl carbonate) -21-methane sulfonate.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chloro benzenesulfonyl chloride in place of methane sulfonyl chloride results in the corresponding 6α-fluoro dexamethasone 17- (ethyl carbonate) -21-P-toluene sulfonate or 6α- Fluoro dexamethasone 17- (ethyl carbonate) -21-P-chloro benzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1668079호에 따라서 6α-플루오로 덱사메타손 및 테트라에틸 오르토 카보네이트로 부터 제조한다.c) 6α-fluoro dexamethasone diethyl ortho carbonate (Rf first required in the reaction)

0.6) is prepared from 6α-fluoro dexamethasone and tetraethyl ortho carbonate according to Federal Republic of Germany Patent No. 1668079.

0.4)로 가수분해시킨다.Subsequently, the aforementioned compound was added to 6α-fluoro dexamethasone 17- (ethyl carbonate) (Rf by the method described in Example 1c).

0.4).

Example 34

a) 1 g betamethasone 17- (ethyl carbonate) in place of methyl chloromate

1) 0.8 ml methyl chloroformate and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) The product is reacted with 1.3 ml of cyclopentyl propionyl chloride by the method described in Example 4a).

In each case

1) betamethasone 17- (ethyl carbonate) -21- (methyl carbonate),

2) betamethasone 17- (ethyl carbonate) -21- (ethyl carbonate),

3) betamethasone 17- (ethyl carbonate) -21- (n-propyl carbonate),

4) betamethasone 17- (ethyl carbonate) -21- (n-butyl carbonate),

5) betamethasone 17- (ethyl carbonate) -21- (isopropyl carbonate),

6) betamethasone 17- (ethyl carbonate) -21- (isobutyl carbonate),

7) betamethasone 17- (ethyl carbonate) -21-acetate,

8) betamethasone 17- (ethyl carbonate) -21-propionate,

9) betamethasone 17- (ethyl carbonate) -21-butyrate,

10) betamethasone 17- (ethyl carbonate) -21-valorate,

11) betamethasone 17- (ethyl carbonate) -21-cyclopropane carboxylate and

12) Obtain betamethasone 17- (ethyl carbonate) -21-cyclopentyl propionate.

b) 3 g of betamethasone 17- (ethyl carbonate) is reacted with methanesulfonyl chloride by the method described in Example 2f) to complete the product. After crystallization from ether, beclomethasone 17- (ethyl carbonate) -21-methane sulfonate is obtained.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzene sulfonyl chloride instead of methane sulfonyl chloride results in the corresponding betamethasone 17- (ethyl carbonate) -21-P-toluene sulfonate or 17- (ethyl carbonate) -21-P-chloro benzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1668079호에 따라서 베타메타손 및 테트라에틸 오르토 카보네이트로 부터 제조한다. 계속해서, 전술한 화합물을 실시예 1c)에 따른 방법으로 가수분해하여 베타메타손 17-(에틸 카보네이트)(Rf

0.4)를 얻는다.c) betamethasone diethyl ortho carbonate (Rf)

0.6) is prepared from betamethasone and tetraethyl ortho carbonate in accordance with Federal Patent No. 1668079. Subsequently, the aforementioned compound was hydrolyzed by the method according to Example 1c) to betamethasone 17- (ethyl carbonate) (Rf

0.4).

Example 35

a) 1 g of 6α-fluoro-prednisolone 17- (ethyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) The product is reacted with 1.3 ml of cyclopentylpropionyl chloride by the method described in Example 4a).

In each case

1) 6α-fluoroprednisolone 17- (ethyl carbonate) -21- (methyl carbonate) -la (methyl carbonate

2) 6α-fluoro-prednisolone 17- (ethyl carbonate) -21- (ethyl carbonate),

3) 6α-fluoro-prednisolone 17- (ethyl carbonate) -21- (n-propyl carbonate),

4) 6α-fluoro-prednisolone 17- (ethyl carbonate) -21- (n-butyl carbonate),

5) 6α-fluoro-prednisolone 17- (ethyl carbonate) -21- (isopropyl carbonate),

6) 6α-fluoro-prednisolone 17- (ethyl carbonate) -21- (isobutyl carbonate),

7) 6α-fluoro-prednisolone 17- (ethyl carbonate) -21-acetate,

8) 6α-fluoro-prednisolone 17- (ethyl carbonate) -21-propionate,

9) 6α-fluoro-prednisolone 17- (ethyl carbonate) -21-butyrate,

10) 6α-fluoro-prednisolone 17- (ethyl carbonate) -21-valorate,

11) 6α-fluoro-prednisolone 17- (ethyl carbonate) -21-cyclopropane carboxylate and

12) 6α-fluoro-prednisolone 17- (ethyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 6α-fluoroprednisolone 17- (ethyl carbonate) are reacted with methanesulfonyl chloride in the manner described in Example 2f) to complete the product. Crystallization from ether gives 6α-fluoro-prednisolone 17- (ethyl carbonate) -21-methane sulfonate.

If equimolar amounts of P-toluene sulfonyl chloride or P-chloro benzenesulfonyl chloride are used instead of methane sulfonyl chloride, the corresponding 6α-fluoro-prednisolone 17- (ethyl carbonate) -21-P-toluene sulfonate or 6α- Fluoro-Prednisolone 17- (ethyl carbonate) -21-P-chloro benzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 따라 6α-플루오로-프레드니솔론 및 테트라에틸 오르토 카보네이트로 부터 수득한다.c) 6α-fluoroprednisolone diethyl ortho carbonate (Rf first required in the reaction)

0.6) is obtained from 6α-fluoro-prednisolone and tetraethyl ortho carbonate according to Federal Republic of Germany Patent No. 1,668,079.

0.4)를 얻는다.The compound described above was then hydrolyzed by the method according to example 1c) to give 6α-fluoro-prednisolone 17- (ethyl carbonate) (Rf

0.4).

Example 36

a) 1 g of 16α- or P-methyl-prednisolone 17- (ethyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) The product is reacted with 1.3 ml of cyclopentyl propionyl chloride by the method described in Example 4a).

In each case

1) 16α- or β-methylprednisolone 17- (ethyl carbonate) -21- (methyl carbonate),

2) 16α- or β-methylprednisolone 17- (ethyl carbonate) -21- (ethyl carbonate),

3) 16α- or β-methylprednisolone 17- (ethyl carbonate) -21- (n-propyl carbonate),

4) 16α- or β-methylprednisolone 17- (ethyl carbonate) -21- (n-butyl carbonate),

5) 16α- or β-methylprednisolone 17- (ethyl carbonate) -21- (isopropyl carbonate),

6) 17α- or β-methylprednisolone 17- (ethyl carbonate) -21- (isobutyl carbonate),

7) 16α- or β-methylprednisolone 17- (ethyl carbonate) -21-acetate,

8) 16α- or β-methylprednisolone 17- (ethyl carbonate) -21-propionate,

9) 16α- or β-methylprednisolone 17- (ethyl carbonate) -21-butyrate,

10) 16α- or β-methylprednisolone 17- (ethyl carbonate) -21-valorate,

11) 16α- or β-methylprednisolone 17- (ethyl carbonate) -21-cyclopropane carboxylate and

12) 16a- or β-methylprednisolone 17- (ethyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 16α- or β-methylprednisolone 17- (ethyl carbonate) are reacted with methanesulfonyl chloride in the manner described in Example 2f) to complete the product. Crystallization from ether gives 16α- or β-methylprednisolone 17- (ethyl carbonate) -21-methane sulfonate.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chloro benzenesulfonyl chloride instead of methane sulfonyl chloride results in the corresponding 16α- or β-methyl-prednisolone 17- (ethyl carbonate) -21-P-toluene sulfonate Or 16α- or β-methylprednisolone 17- (ethyl carbonate) -21-P-chloro benzene sulfonate.

0.6)는 독일연방공화국 특허 제1,668,079호에 따라 16α-또는 β-메틸프레드니솔론 및 테트라에틸 오르토 카보네이트로 부터 제조한다.c) 16α- or β-methylprednisolone diethyl ortho carbonate (Rf initially required in the reaction)

0.6) is prepared from 16α- or β-methylprednisolone and tetraethyl ortho carbonate according to Federal Republic of Germany Patent No. 1,668,079.

0.4)를 얻는다.Subsequently, the compound described above was hydrolyzed by the method according to Example 1c) to 16α- or β-methylprednisolone 17- (ethyl carbonate) (Rf

0.4).

Example 37

a) 1 g of 6α, 16α- or β-dimethylprednisolone-17- (ethyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) The product is reacted with 1.3 ml of cyclopentyl propionyl chloride by the method described in Example 4a).

In each case

1) 6α, 16α- or β-dimethyl-prednisolone 17- (ethyl carbonate) -21- (methyl carbonate),

2) 6α, 16α- or β-dimethyl-prednisolone 17- (ethyl carbonate) -21- (ethyl carbonate),

3) 6α, 16α- or β-dimethyl-prednisolone 17- (ethyl carbonate) -21- (n-propyl carbonate),

4) 6α, 16α- or β-dimethyl-prednisolone 17- (ethyl carbonate) -21- (n-butyl carbonate),

5) 6α, 16α- or β-dimethyl-prednisolone 17- (ethyl carbonate) -21- (isopropyl carbonate),

6) 6α, 16α- or β-dimethyl-prednisolone 17- (ethyl carbonate) -21- (isobutyl carbonate),

7) 6α, 16α- or β-dimethyl-prednisolone 17- (ethyl carbonate) -21-acetate,

8) 6α, 16α- or β-dimethyl-prednisolone 17- (ethyl carbonate) -21-propionate,

9) 6α, 16α- or β-dimethyl-prednisolone 17- (ethyl carbonate) -21-butyrate,

10) 6α, 16α- or β-dimethyl-prednisolone 17- (ethyl carbonate) -21-valorate,

11) 6α, 16α- or β-dimethyl-prednisolone 17- (ethyl carbonate) -21-cyclopropane carboxylate and

12) 6α, 16α- or β-dimethyl-prednisolone 17- (ethyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 6α, 16α- or β-dimethyl-prednisolone 17- (ethyl carbonate) are reacted with methanesulfonyl chloride in a similar manner to Example 2f) and the product is completed. Crystallization from ether gives 6α, 16α- or β-dimethyl-prednisolone 17- (ethyl carbonate) -21-methane sulfonate.

The use of equimolar amounts of P-toluene sulfonyl chloride instead of methane sulfonyl chloride results in the corresponding 6α, 16α- or β-dimethyl-prednisolone 17- (ethyl carbonate) -21-P-toluene sulfonate or 6α, 16α-or β-dimethyl-prednisolone 17- (ethyl carbonate) -21-P-chloro benzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 따라 6α,16α-또는 β-디메틸-프레드니솔론 및 테트라에틸 오르토 카보네이트로 부터 수득된다.c) 6α, 16α- or β-dimethyl-prednisolone diethyl ortho carbonate (Rf initially required in the reaction)

0.6) is obtained from 6α, 16α- or β-dimethyl-prednisolone and tetraethyl ortho carbonate in accordance with Federal Patent No. 1,668,079.

0.4)를 얻는다.Subsequently, the first mentioned compound was hydrolyzed by the method described in Example 1c) to give 6α, 16α- or β-dimethyl-prednisolone 17- (ethyl carbonate) (Rf

0.4).

Example 38

a) 1 g of 9α-chloro-16α-methyl-prednisolone 17- (ethyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) The product is reacted with 1.3 ml of cyclopentyl propionyl chloride by the method described in Example 4a).

In each case

1) 9α-chloro-16α-methyl-prednisolone 17- (ethyl carbonate) -21- (methyl carbonate),

2) 9α-chloro-16α-methyl-prednisolone 17- (ethyl carbonate) -21- (ethyl carbonate),

3) 9α-chloro-16α-methyl-prednisolone 17- (ethyl carbonate) -21- (n-propyl carbonate),

4) 9α-chloro-16α-methyl-prednisolone 17- (ethyl carbonate) -21- (n-butyl carbonate),

5) 9α-chloro-16α-methyl-prednisolone 17- (ethyl carbonate) -21- (isopropyl carbonate),

6) 9α-chloro-16α-methyl-prednisolone 17- (ethyl carbonate) -21- (isobutyl carbonate),

7) 9α-chloro-16α-methyl-prednisolone 17- (ethyl carbonate) -21-acetate,

8) 9α-chloro-16α-methyl-prednisolone 17- (ethyl carbonate) -21-propionate,

9) 9α-chloro-16α-methyl-prednisolone 17- (ethyl carbonate) -21-butyrate,

10) 9α-chloro-16α-methyl-prednisolone 17- (ethyl carbonate) -21-valorate,

11) 9α-chloro-16α-methyl-prednisolone 17- (ethyl carbonate) -21-cyclopropane carboxylate and

12) 9α-chloro-16α-methyl-prednisolone 17- (ethyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 9α-chloro-16α-methyl-prednisolone 17- (ethyl carbonate) are reacted with methanesulfonyl chloride in the manner described in Example 2f) to complete the product. Crystallization from ether gives 9α-chloro-16α-methyl-prednisolone 17- (ethyl carbonate) -21-methane sulfonate.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzene sulfonyl chloride in place of methane sulfonyl chloride provides the corresponding chloromethyl prednisolone ethyl carbonate toluene sulfonate or 6α-chloro-16α-methyl-prednisolone 17- (ethyl Carbonate) -21-P-chloro benzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 따라 6α-클로로-16α-메틸-프레드니솔론 및 테트라에틸 오르토 카보네이트로 부터 제조한다.c) 6α-chloro-16α-methyl-prednisolone diethyl ortho carbonate (Rf first required for reaction)

0.6) is prepared from 6α-chloro-16α-methyl-prednisolone and tetraethyl ortho carbonate in accordance with Federal Patent No. 1,668,079.

0.4)로 가수분해시킨다.Subsequently, the aforementioned compound was added to 6α-chloro-16α-methyl-prednisolone 17- (ethyl carbonate) (Rf by the method described in Example 1c).

0.4).

Example 39

a) 1 g of 9α-chloro-prednisolone 17- (ethyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) The product is reacted with 1.3 ml of cyclopentyl propionyl chloride by the method described in Example 4a).

In each case

1) 9α-chloro-prednisolone 17- (ethyl carbonate) -21- (methyl carbonate),

2) 9α-chloro-prednisolone 17- (ethyl carbonate) -21- (ethyl carbonate),

3) 9α-chloro-prednisolone 17- (ethyl carbonate) -21- (n-propyl carbonate),

4) 9α-chloro-prednisolone 17- (ethyl carbonate) -21- (n-butyl carbonate),

5) 9α-chloro-prednisolone 17- (ethyl carbonate) -21- (isopropyl carbonate),

6) 9α-chloro-prednisolone 17- (ethyl carbonate) -21- (isobutyl carbonate),

7) 9α-chloro-prednisolone 17- (ethyl carbonate) -21-acetate,

8) 9α-chloro-prednisolone 17- (ethyl carbonate) -21-propionate,

9) 9α-chloro-prednisolone 17- (ethyl carbonate) -21-butyrate,

10) 9α-chloro-prednisolone 14- (ethyl carbonate) -21-valorate,

11) 9α-chloro-prednisolone 17- (ethyl carbonate) -21-cyclopropane carboxylate and

12) 9α-chloro-prednisolone 17- (ethyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 9α-chloro-prednisolone 17- (ethyl carbonate) are reacted with methanesulfonyl chloride in the manner described in Example 2f) to complete the product. Crystallization from ether gives 9α-chloro-prednisolone 17- (ethyl carbonate) -21-methane sulfonate.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzene sulfonyl chloride in place of methane sulfonyl chloride results in the corresponding 9α-chloro-prednisolone 17- (ethyl carbonate) -21-P-toluenesulfonate or 9α- Chloro-prednisolone 17- (ethyl carbonate) -21-P-chlorobenzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 따라서 9α-클로로-프레드니솔론 및 테트라에틸 오르토 카보네이트로부터 제조한다.c) 9α-chloro-prednisolonediethyl ortho carbonate (Rf required for the first time in the reaction)

0.6) is prepared from 9α-chloro-prednisolone and tetraethyl ortho carbonate in accordance with Federal Patent No. 1,668,079.

0.4)를 얻는다.Subsequently, the aforementioned compound was hydrolyzed by the method described in Example 1c) to give 9α-chloro-prednisolone 17- (ethyl carbonate) (Rf

0.4).

Example 40

a) 1 g of prednisolone 17- (n-propyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.9 ml of butyryl chloride,

8) 1 ml of valeryl chloride,

9) 1 ml of cyclopropane carboxylic acid chloride and

10) Reaction with 1.3 ml of cyclopentyl propionyl chloride in the manner described in Example 4a) to complete the product.

In each case

1) prednisolone 17- (n-propyl carbonate) -21- (methyl carbonate),

2) prednisolone 17- (n-propyl carbonate) -21- (ethyl carbonate),

3) prednisolone 17- (n-propyl carbonate) -21- (n-propyl carbonate),

4) prednisolone 17- (n-propyl carbonate) -21- (n-butyl carbonate),

5) prednisolone 17- (n-propyl carbonate) -21- (isopropyl carbonate),

6) prednisolone 17- (n-propyl carbonate) -21- (isobutyl carbonate),

7) prednisolone 17- (n-propyl carbonate) -21-butyrate,

8) prednisolone 17- (n-propyl carbonate) -21-valorate,

9) prednisolone 17- (n-propyl carbonate) -21-cyclopropanecarboxylate and

10) Prednisolone 17- (n-propyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of prednisolone 17- (n-propyl carbonate) are reacted with methanesulfonyl chloride in the manner described in Example 2f) to complete the product. 17- (n-propyl carbonate) -21-methane sulfonate is obtained after crystallization from ether.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzene sulfonyl chloride in place of methane sulfonyl chloride results in the corresponding prednisolone 17- (n-propyl carbonate) -21-P-toluene sulfonate or prednisolone 17- ( n-propyl carbonate) -21-P-chlorobenzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 따라서 프레드니솔론 및 테트라-(n-프로필) 오르토 카보네이트로부터 제조된다.c) prednisolone di (n-propyl) orthocarbonate (Rf)

0.6) are prepared from prednisolone and tetra- (n-propyl) ortho carbonate according to Federal Republic of Germany Patent No. 1,668,079.

0.4)를 얻는다.Subsequently, the above-mentioned compound was hydrolyzed by the method described in Example 1c) to prednisolone 17- (n-propyl carbonate) (Rf

0.4).

Example 41

a) 1 g of prednisolone 17- (n-propyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) React the product with 1.3 ml of cyclopentylpropionyl chloride in the manner described in Example 4a).

In each case

1) prednisolone 17- (n-propyl carbonate) -21- (methyl carbonate),

2) prednisolone 17- (n-propyl carbonate) -21- (ethyl carbonate),

3) prednisolone 17- (n-propyl carbonate) -21- (n-propyl carbonate),

4) prednisolone 17- (n-propyl carbonate) -21- (n-butyl carbonate),

5) prednisolone 17- (n-propyl carbonate) -21- (isopropyl carbonate),

6) prednisolone 17- (n-propyl carbonate) -21- (isobutyl carbonate),

7) prednisolone 17- (n-propyl carbonate) -21-acetate,

8) prednisolone 17- (n-propyl carbonate) -21-propionate,

9) prednisolone 17- (n-propyl carbonate) -21-butyrate,

10) prednisolone 17- (n-propyl carbonate) -21-valorate,

11) prednisolone 17- (n-propyl carbonate) -21-cyclopropanecarboxylate and

12) Prednisolone 17- (n-propyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of prednisolone 17- (n-propyl carbonate) are reacted with methanesulfonyl chloride in the manner described in Example 2f) to complete the product. 17- (n-propyl carbonate) -21-methane sulfonate is obtained after crystallization from ether.

The use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methane sulfonyl chloride gives the corresponding prednisolone 17- (n-propyl carbonate) -21-P-toluene sulfonate or prednisolone 17- ( n-propyl carbonate) -21-P-chlorobenzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 따라 프레드니솔론 및 테트라-(n-프로필) 오르토 카보네이트로부터 제조한다. 계속해서, 전술한 화합물을 실시예 1c)에 기술된 방법으로 가수분해시켜 17-(n-프로필 카보네이트)(Rf

0.4)를 얻는다.c) prednisolone di- (n-propyl) orthocarbonate (Rf)

0.6) are prepared from prednisolone and tetra- (n-propyl) ortho carbonate according to Federal Republic of Germany Patent No. 1,668,079. Subsequently, the aforementioned compound was hydrolyzed by the method described in Example 1c) to give 17- (n-propyl carbonate) (Rf

0.4).

Example 42

a) 1 g of cortisone 17- (n-propyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride

12) React the product with 1.3 ml of cyclopentylpropionyl chloride in the manner described in Example 4a).

In each case

1) Cortisone 17- (n-propyl carbonate) -21- (methyl carbonate),

2) cortisone 17- (n-propyl carbonate) -21- (ethyl carbonate),

3) cortisone 17- (n-propyl carbonate) -21- (n-propyl carbonate),

4) cortisone 17- (n-propyl carbonate) -21- (n-butyl carbonate),

5) cortisone 17- (n-propyl carbonate) -21- (isopropyl carbonate),

6) cortisone 17- (n-propyl carbonate) -21- (isobutyl carbonate),

7) cortisone 17- (n-propyl carbonate) -21-acetate,

8) cortisone 17- (n-propyl carbonate) -21-propionate,

9) cortisone 17- (n-propyl carbonate) -21-butyrate,

10) cortisone 17- (n-propyl carbonate) -21-valorate,

11) Cortisone 17- (n-propyl carbonate) -21-cyclopropane carboxylate and

12) Cortisone 17- (n-propyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of Cortisone 17- (n-propyl carbonate) is reacted with methanesulfonyl chloride by the method described in Example 2f) to complete the product.

After crystallization from ether, cortisone 17- (n-propyl carbonate) -21-methane sulfonate is obtained.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzene sulfonyl chloride instead of methane sulfonyl chloride results in the corresponding cortisone 17- (n-propyl carbonate) -21-P-toluenesulfonate or cortisone 17- ( n-propyl carbonate) -21-P-chlorobenzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 따라 코르티니손 및 테트라(n-프로필) 오르토 카보네이트로부터 제조된다.c) Cortisone di (n-propyl) orthocarbonate (Rf initially required for the reaction)

0.6) are made from cortinone and tetra (n-propyl) ortho carbonate according to Federal Republic of Germany Patent No. 1,668,079.

0.4)로 실시예 d)에 기술된 방법으로 가수분해시킨다.Subsequently, the aforementioned compound was added to cortisone 17- (n-propyl carbonate) (Rf

0.4) to hydrolysis in the manner described in Example d).

Example 43

a) 1 g cortisol 17- (n-propyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0,8 ml of acetyl chloride,

8) 0.9 ml of butyryl chloride,

9) 1 ml of valeryl chloride,

10) 1 ml of cyclopropane carboxylic acid chloride and

11) Reaction with 1.3 ml of cyclopentyl propionyl chloride in the manner described in Example 4a) to complete the product.

In each case

1) Cortisol 17- (n-propyl carbonate) -21- (methyl carbonate),

2) cortisol 17- (n-propyl carbonate) -21- (ethyl carbonate),

3) cortisol 17- (n-propyl carbonate) -21- (n-propyl carbonate),

4) cortisol 17- (n-propyl carbonate) -21- (n-butyl carbonate),

5) Cortisol 17- (n-propyl carbonate) -21- (isopropyl carbonate),

6) cortisol 17- (n-propyl carbonate) -21- (isobutyl carbonate),

7) cortisol 17- (n-propyl carbonate) -21-acetate,

8) Cortisol 17- (n-propyl carbonate) -21-butyrate.

9) cortisol 17- (n-propyl carbonate) -21-balarate,

10) Cortisol 17- (n-propyl carbonate) -21-cyclopropanecarboxylate and

11) Cortisol 17- (n-propyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of Cortisol 17- (n-propyl carbonate) is reacted with methanesulfonyl chloride in the manner described in Example 2f) and the product is completed. After crystallization from ether, cortisol 17- (n-propyl carbonate) -21-methane sulfonate is obtained.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride in place of methane sulfonyl chloride results in the corresponding cortisol 17- (n-propyl carbonate) -21-P-toluene sulfonate or cortisol 17- ( n-propyl carbonate) -21-P-chlorobenzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 따라 코르티솔 및 테트라-(n-프로필) 오르토 카보네이트로부터 제조된다.c) Cortisol di- (n-propyl) orthocarbonate (Rf required for the first time in the reaction)

0.6) is made from cortisol and tetra- (n-propyl) ortho carbonate according to Federal Republic of Germany Patent No. 1,668,079.

0.4)로 실시예 1c)에 기술된 방법으로 가수분해시킨다.Subsequently, the above-mentioned compound is cortisol 17- (n-propyl carbonate) (Rf

0.4) to hydrolysis in the manner described in Example 1c).

Example 44

a) 1 g of beclomethasone 17- (n-propylcarbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) The product is reacted with 1.3 ml of cyclopentyl propionyl chloride by the method described in Example 4a).

In each case

1) Beckro metason 17- (n-propyl carbonate) -21- (methyl carbonate),

2) Beckro metason 17- (n-propyl carbonate) -21- (ethyl carbonate),

3) Beckro metason 17- (n-propyl carbonate) -21- (n-propyl carbonate),

4) Beckro metason 17- (n-propyl carbonate) -21- (n-butyl carbonate),

5) Beckro metason 17- (n-propyl carbonate) -21- (isopropyl carbonate),

6) Beckro metason 17- (n-propyl carbonate) -21- (isobutyl carbonate),

7) Beckro metason 17- (n-propyl carbonate) -21-acetate,

8) Beckro metason 17- (n-propyl carbonate) -21-propionate,

9) Beckro metason 17- (n-propyl carbonate) -21-butyrate,

10) Beckro metason 17- (n-propyl carbonate) -21-balarate,

11) Beckro metason 17- (n-propyl carbonate) -21-cyclopropane carboxylate and

12) Obtain becromethasone 17- (n-propyl carbonate) -21-cyclopentyl propionate.

b) 3 g of Beckcromethasone 17- (n-propyl carbonate) are reacted with methanesulfonyl chloride in the manner described in Example 2f) to complete the product. After crystallization from ether, Velcro metason 17- (n-propyl carbonate) -21-methane sulfonate is obtained.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzene sulfonyl chloride in place of methane sulfonyl chloride results in the corresponding Becker metason 17- (n-propyl carbonate) -21-P-toluenesulfonate or Beck Rho metason 17- (n-propyl carbonate) -21-P-chlorobenzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 따라 베크로 메타손 및 테트라-(n-프로필) 오르토 카보네이트로부터 제조된다.c) Beckomethasone di- (n-propyl) orthocarbonate (Rf initially required in the reaction)

0.6) is prepared from Beckro metason and tetra- (n-propyl) ortho carbonate according to Federal Republic of Germany Patent No. 1,668,079.

0.4)로 실시예 1c)에 기술된 방법으로 가수분해시킨다.Subsequently, the above-mentioned compound was replaced with becromethasone 17- (n-propyl carbonate) (Rf

0.4) to hydrolysis in the manner described in Example 1c).

Example 45

a) 1 g of 6α-fluorodexamethasone 17- (n-propyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) React with 1.3 ml of cyclopentyl propionyl chloride according to the method described in Example 4a) to complete the product.

In each case

1) 6α-fluorodexamethasone 17- (n-propyl carbonate) -21- (methyl carbonate),

2) 6α-fluorodexamethasone 17- (n-propyl carbonate) -21- (ethyl carbonate),

3) 6α-fluorodexamemethasone 17- (n-propyl carbonate) -21- (n-propyl carbonate),

4) 6α-fluorodexamethasone 17- (n-propyl carbonate) -21- (n-butyl carbonate),

5) 6α-fluorodexamethasone 17- (n-propyl carbonate) -21- (isopropyl carbonate),

6) 6α-fluorodexamethasone 17- (n-propyl carbonate) -21- (isobutyl carbonate),

7) 6α-fluorodexamemethasone 17- (n-propyl carbonate) -21-acetate,

8) 6α-fluorodexamethasone 17- (n-propyl carbonate) -21-propionate,

9) 6α-fluorodexamethasone 17- (n-propyl carbonate) -21-butyrate,

10) 6α-fluorodexamethasone 17- (n-propyl carbonate) -21-valorate,

11) 6α-fluorodexamethasone 17- (n-propyl carbonate) -21-cyclopropane carboxylate and

12) 6α-fluorodexamethasone 17- (n-propyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 6α-fluorodexamethasone 17- (n-propyl carbonate) are reacted with methanesulfonyl chloride in the manner described in Example 2f) to complete the product.

After crystallization from ether, 6α-fluorodexamemethasone 17- (n-propyl carbonate) -21-methane sulfonate is obtained.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methane sulfonyl chloride results in the corresponding 6α-fluorodexamemethasone 17- (n-propyl carbonate) -21-P-toluenesulfonate or Obtain 6α-fluorodexamemethasone 17- (n-propyl carbonate) -21-P-chlorobenzene sulfonate.

0.6)는 독일연방공화국 특허 제1,668,079호에 따라 6α-플루오로덱사메타손 및 테트라-(n-프로필) 오르토 카보네이트로부터 제조된다.c) 6α-fluorodexamemethasone di (n-propyl) orthocarbonate (Rf initially required for the reaction)

0.6) is prepared from 6α-fluorodexamemethasone and tetra- (n-propyl) ortho carbonate according to Federal Republic of Germany Patent No. 1,668,079.

0.4)로 실시예 1c)에 기술된 방법으로 가수분해한다.Subsequently, the compounds mentioned are 6α-fluorodexamemethasone 17- (n-propyl carbonate) (Rf

0.4) to hydrolysis by the method described in Example 1c).

Example 46

a) 1 g of betamethasone 17- (n-propyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) The product is reacted with 1.3 ml of cyclopentyl propionyl chloride by the method described in Example 4a).

In each case

1) betamethasone 17- (n-propyl carbonate) -21- (methyl carbonate),

2) betamethasone 17- (n-propyl carbonate) -21- (ethyl carbonate),

3) betamethasone 17- (n-propyl carbonate) -21- (n-propyl carbonate),

4) betamethasone 17- (n-propyl carbonate) -21- (n-butyl carbonate),

5) betamethasone 17- (n-propyl carbonate) -21- (isopropyl carbonate),

6) betamethasone 17- (n-propyl carbonate) -21- (isobutyl carbonate),

7) betamethasone 17- (n-propyl carbonate) -21-acetate,

8) betamethasone 17- (n-propyl carbonate) -21-propionate,

9) betamethasone 17- (n-propyl carbonate) -21-butyrate,

10) betamethasone 17- (n-propyl carbonate) -21-valorate,

11) betamethasone 17- (n-propyl carbonate) -21-cyclopropane carboxylate and

12) Betamethasone 17- (n-propyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of betamethasone 17- (n-propyl carbonate) is reacted with methanesulfonyl chloride in the manner described in Example 2f) to complete the product.

After crystallization from ether, betamethasone 17- (n-propyl carbonate) -21-methane sulfonate is obtained.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methane sulfonyl chloride results in the corresponding betamethasone 17- (n-propyl carbonate) -21-P-toluenesulfonate or betamethasone 17- ( n-propyl carbonate) -21-P-chlorobenzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 따라 베타메타손 및 테트라-(n-프로필) 오르토 카보네이트로부터 제조된다.c) Betamethasone di- (n-propyl) orthocarbonate (Rf initially required in the reaction)

0.6) are prepared from betamethasone and tetra- (n-propyl) ortho carbonates according to Federal Republic of Germany Patent No. 1,668,079.

0.4)로 실시예 1c)에 기술된 방법으로 가수분해시킨다.Subsequently, the aforementioned compound was converted to betamethasone 17- (n-propyl carbonate) (Rf

0.4) to hydrolysis in the manner described in Example 1c).

Example 47

a) 1 g of 6α-fluoro-prednisolone 17- (n-propyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclo-propane carboxylic acid chloride and

12) 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete the product to yield the corresponding

1) 6α-fluoro-prednisolone 17- (n-propyl carbonate) -21- (methyl carbonate),

2) 6α-fluoro-prednisolone 17- (n-propyl carbonate) -21- (n-propyl carbonate),

4) 6α-fluoro-prednisolone 17- (n-propyl carbonate) -21- (n-butyl carbonate),

5) 6α-fluoro-prednisolone 17- (n-propyl carbonate) -21- (isopropyl carbonate),

6) 6α-fluoro-prednisolone 17- (n-propyl carbonate) -21- (isobutyl carbonate),

7) 6α-fluoro-prednisolone 17- (n-propyl carbonate) -21-acetate,

8) 6α-fluoro-prednisolone 17- (n-propyl carbonate) -21-propionate,

9) 6α-fluoro-prednisolone 17- (n-propyl carbonate) -21-butyrate,

10) 6α-fluoro-prednisolone 17- (n-propyl carbonate) -21-valorate,

11) 6α-fluoro-prednisolone 17- (n-propyl carbonate) -21-cyclopropane carboxylate and

12) 6α-fluoro-prednisolone 17- (n-propyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 6α-fluoro-prednisolone 17- (n-propyl carbonate) was reacted with methanesulfonyl chloride as in Example 2f) and completed and crystallized with ether to give 6α-fluoro-prednisolone 17- (n- Propyl carbonate) -21-methane sulfonate is obtained.

If equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride are used instead of methanesulfonyl chloride, the corresponding 6α-fluoro-prednisolone 17- (n-propyl carbonate) -21-P-toluene sulfonate, respectively Or 6α-fluoro-prednisolone 17- (n-propyl carbonate) -21-P-chlorobenzene sulfonate.

0.6)는 독일연방공화국 특허 제1,668,079호에 방법에 따라서 6α-플루오로-프레드니솔론 및 테트라-(n-프로필) 오르토 카보네이트로부터 제조한다. 이어서, 처음에 언급된 화합물을 실시예 1c)의 방법으로 가수분해 시켜 6α-플루오로-프레드니솔론 17-(n-프로필 카보네이트)(Rf

0.4)를 제조한다.c) 6α-fluoro-prednisolone di- (n-propyl) orthocarbonate used for the first time in the reaction (Rf

0.6) is prepared from 6α-fluoro-prednisolone and tetra- (n-propyl) ortho carbonate according to the method of German Patent No. 1,668,079. The compound mentioned initially was then hydrolyzed by the method of Example 1c) to give 6α-fluoro-prednisolone 17- (n-propyl carbonate) (Rf

0.4) is prepared.

Example 48

a) 1 g of 16α- or β-methyl-prednisolone 17- (n-propyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate, and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) react with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete the product in each case

1) 16α- or β-methyl-prednisolone 17- (n-propyl carbonate) -21- (methyl carbonate),

2) 16α- or β-methyl-prednisolone 17- (n-propyl carbonate) -21- (ethyl carbonate),

3) 16α- or β-methyl-prednisolone 17- (n-propyl carbonate) -21- (n-propyl carbonate),

4) 16α- or β-methyl-prednisolone 17- (n-propyl carbonate) -21- (n-butyl carbonate),

5) 16α- or β-methyl-prednisolone 17- (n-propyl carbonate) -21- (isopropyl carbonate),

6) 16α- or β-methyl-prednisolone 17- (n-propyl carbonate) -21- (isobutyl carbonate),

7) 16α- or β-methyl-prednisolone 17- (n-propyl carbonate) -21-acetate,

8) 16α- or β-methyl-prednisolone 17- (n-propyl carbonate) -21-propionate,

9) 16α- or β-methyl-prednisolone 17- (n-propyl carbonate) -21-butyrate,

10) 16α- or β-methyl-prednisolone 17- (n-propyl carbonate) -21-valorate,

11) 16α- or β-methyl-prednisolone 17- (n-propyl carbonate) -21-cyclopropanecarboxylate and

12) 6α- or β-methyl-prednisolone 17- (n-propyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 16α- or β-methyl-prednisolone 17- (n-propyl carbonate) is reacted with methanesulfonyl chloride as in Example 2f) and completed and crystallized with ether to give 16α- or β-methyl-prednisolone 17 -(n-propyl carbonate) -21-methane sulfonate is obtained.

Reaction of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methanesulfonyl chloride results in the corresponding 16α- or β-methyl-prednisolone 17- (n-propyl carbonate) -21-P- Toluenesulfonate or 16α- or β-methyl-prednisolone 17- (n-propyl carbonate) -21-P-chlorobenzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 제시된 바에 따라 16α, 또는 β-메틸-프레드니솔론 과 테트라(n-프로필)오르토 카보네이트로부터 제조한다.c) 16α, or β-methyl-prednisolone di- (n-propyl) orthocarbonate (Rf required preferentially for the reaction)

0.6) is prepared from 16α, or β-methyl-prednisolone and tetra (n-propyl) ortho carbonate, as set forth in German Patent No. 1,668,079.

0.4)를 제조한다.The first mentioned compound was then hydrolyzed as in Example 1c) to 16α, or β-methyl-prednisolone 17- (n-propyl carbonate) (Rf

0.4) is prepared.

Example 49

a) 1 g of 6α, 16α- or β-dimethyl-prednisolone 17- (n-propyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) Reaction with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) corresponds in each case

1) 6α, 16α- or β-dimethyl-prednisolone 17- (n-propyl carbonate) -21- (methyl carbonate),

2) 6α, 16α- or β-dimethyl-prednisolone 17- (n-propyl carbonate) -21- (ethyl carbonate),

3) 6α, 16α- or β-dimethyl-prednisolone 17- (n-propyl carbonate) -21- (n-propyl carbonate),

4) 6α, 16α- or β-dimethyl-prednisolone 17- (n-propyl carbonate) -21- (n-butyl carbonate),

5) 6α, 16α- or β-dimethyl-prednisolone 17- (n-propyl carbonate) -21- (isopropyl carbonate),

6) 6α, 16α- or β-dimethyl-prednisolone 17- (n-propyl carbonate) -21- (isobutyl carbonate),

7) 6α, 16α- or β-dimethyl-prednisolone 17- (n-propyl carbonate) -21-acetate,

8) 6α, 16α- or β-dimethyl-prednisolone 17- (n-propyl carbonate) -21-propionate,

9) 6α, 16α- or β-dimethyl-prednisolone 17- (n-propyl carbonate) -21-butyrate,

10) 6α, 16α- or β-dimethyl-prednisolone 17- (n-propyl carbonate) -21-valorate,

11) 6α, 16α- or β-dimethyl-prednisolone 17- (n-propyl carbonate) -21-cyclopropanecarboxylate and

12) 6α, 16α- or β-dimethyl-prednisolone 17- (n-propyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 6α, 16α or β-dimethyl-prednisolone 17- (n-propyl carbonate) are reacted with methanesulfonyl chloride and finished as in Example 2f) and crystallized with ether to give 6α, 16α- or β-dimethyl Prednisolone 17- (n-propyl carbonate) -21-p-methane-sulfonate is obtained.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methanesulfonyl chloride results in the corresponding 6α, 16α- or β-dimethyl-prednisolone 17- (n-propyl carbonate) -21-P Toluenesulfonate or 6α, 16α- or β-dimethyl-prednisolone 17- (n-propyl carbonate) -21-P-chlorobenzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 제시된 바에 따라 6α, 16α-또는 β-디메틸-프레드니솔론 및 테트라-(n-프로필)오르토 카보네이트로부터 제조된다. 이어서 처음 언급된 화합물을 실시예 1c)에서와 같이 가수분해시켜 6α, 16α-또는 β-디메틸-프레드니솔론 17-(n-프로필 카보네이트)(Rf

0.4)를 제조한다.c) 6α, 16α- or β-dimethyl-prednisolone di- (n-propyl) orthocarbonate (Rf required preferentially for the reaction)

0.6) are prepared from 6α, 16α- or β-dimethyl-prednisolone and tetra- (n-propyl) ortho carbonates as set forth in German Patent No. 1,668,079. The first mentioned compound was then hydrolyzed as in Example 1c) to give 6α, 16α- or β-dimethyl-prednisolone 17- (n-propyl carbonate) (Rf

0.4) is prepared.

Example 50

a) 1 g of 9α-chloro-16α-methyl-prednisolone 17- (n-propyl carbonate) in place of methyl chloroformate, respectively

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) React with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete the product so that the corresponding

1) 9α-chloro-16α-methyl-prednisolone 17- (n-propyl carbonate) -21- (methyl carbonate),

2) 9α-chloro-16α-methyl-prednisolone 17- (n-propyl carbonate) -21- (ethyl carbonate),

3) 9α-chloro-16α-methyl-prednisolone 17- (n-propyl carbonate) -21- (n-propyl carbonate),

4) 9α-chloro-16α-methyl-prednisolone 17- (n-propyl carbonate) -21- (n-butyl carbonate),

5) 9α-chloro-16α-dimethyl-prednisolone 17- (n-propyl carbonate) -21- (isopropyl carbonate),

6) 9α-chloro-16α-methyl-prednisolone 17- (n-propyl carbonate) -21- (isobutyl carbonate),

7) 9α-chloro-16α-methyl-prednisolone 17- (n-propyl carbonate) -21-acetate,

8) 9α-chloro-16α-methyl-prednisolone 17- (n-propyl carbonate) -21-propionate,

9) 9α-chloro-16α-methyl-prednisolone 17- (n-propyl carbonate) -21-butyrate,

10) 9α-chloro-16α-methyl-prednisolone 17- (n-propyl carbonate) -21-valorate,

11) 9α-chloro-16α-methyl-prednisolone 17- (n-propyl carbonate) -21-clopropananecarboxylate and

12) 9α-chloro-16α-methyl-prednisolone 17- (n-propyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 9α-chloro-16α-methyl-prednisolone 17- (n-propyl carbonate) was reacted with methanesulfonyl chloride as in Example 2f and completed and crystallized with ether to give 9α-chloro-16α-methyl- Prednisolone 17- (n-propyl carbonate) -21-methane sulfonate is obtained.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methanesulfonyl chloride results in the corresponding 9α-chloro-16α-methyl-prednisolone 17- (n-propyl carbonate) -21-P-toluene Sulfonate or 6α-chloro-16α-methyl-prednisolone 17- (n-propyl carbonate) -21-P-chlorobenzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 제시된 바에 따라 9α-클로로-16α-메틸-프레드니솔론 및 테트라-(n-프로필)오르토 카보네이트로부터 제조한다. 이어서 처음 언급된 화합물을 실시예 1c)에서와 같이 가수분해시켜 9α-클로로-16α-메틸-프레드니솔론 17-(n-프로필 카보네이트)(Rf

0.1)를 제조한다.c) 9α-chloro-16α-methyl-prednisolone di- (n-propyl) orthocarbonate (Rf required preferentially for this reaction)

0.6) is prepared from 9α-chloro-16α-methyl-prednisolone and tetra- (n-propyl) ortho carbonate as set forth in Federal Republic of Germany Patent No. 1,668,079. The first mentioned compound was then hydrolyzed as in Example 1c) to give 9α-chloro-16α-methyl-prednisolone 17- (n-propyl carbonate) (Rf

0.1) is prepared.

Example 51

a) 1 g of 9α-chloro-prednisolone 17- (n-propyl carbonate) in place of methyl chloroformate, respectively

1) 0.8 ml methyl chloroformate and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclo-propane carboxylic acid chloride and

12) Complete the product as in Example 4a) with 1.3 ml of cyclopentyl propionyl chloride to obtain the corresponding

1) 9α-chloro-prednisolone 17- (n-propyl carbonate) -21- (methyl carbonate),

2) 9α-chloro-prednisolone 17- (n-propyl carbonate) -21- (ethyl carbonate),

3) 9α-chloro-prednisolone 17- (n-propyl carbonate) -21- (n-propyl carbonate),

4) 9α-chloro-prednisolone 17- (n-propyl carbonate) -21- (n-butyl carbonate),

5) 9α-chloro-prednisolone 17- (n-propyl carbonate) -21- (isopropyl carbonate),

6) 9α-chloro-prednisolone 17- (n-propyl carbonate) -21- (isobutyl carbonate),

7) 9α-chloro-prednisolone 17- (n-propyl carbonate) -21-acetate,

8) 9α-chloro-prednisolone 17- (n-propyl carbonate) -21-propionate,

9) 9α-chloro-prednisolone 17- (n-propyl carbonate) -21-butyrate,

10) 9α-chloro-prednisolone 17- (n-propyl carbonate) -21-valorate,

11) 9α-chloro-prednisolone 17- (n-propyl carbonate) -21-chloro-propanecarboxylate and

12) 9α-chloro-prednisolone 17- (n-propyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 9α-chloro-prednisolone 17- (n-propyl carbonate) was reacted with methanesulfonyl chloride as in Example 2f) and completed and crystallized with ether to give 9α-chloro-prednisolone 17- (n-propyl carbonate). ) -21-methane sulfonate is obtained.

If equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride are used instead of methanesulfonyl chloride, the corresponding 9α-chloro-prednisolone 17- (n-propyl carbonate) -21-P-toluenesulfonate or 9α Chloro-prednisolone 17- (n-propyl carbonate) -21-P-chlorobenzene sulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 제시된 바에 따라 9α-클로로-프레드니솔론 및 테트라(n-프로필)오르토 카보네이트로부터 제조된다. 이어서 처음에 언급된 화합물을 실시예 1c)에서와 같이 가수분해시켜 9α-클로로-프레드니솔론 17-(n-프로필 카보네이트)(Rf

0.4)를 제조한다.c) 9α-chloro-prednisolone di- (n-propyl) ortho carbonate (Rf required preferentially for this reaction)

0.6) is prepared from 9α-chloro-prednisolone and tetra (n-propyl) ortho carbonate as set forth in German Patent No. 1,668,079. The first mentioned compound was then hydrolyzed as in Example 1c) to give 9α-chloro-prednisolone 17- (n-propyl carbonate) (Rf

0.4) is prepared.

Example 52

a) 1 g of prednisolone 17- (n-butyl carbonate) in place of methyl chloroformate, respectively

1) 0.8 ml methyl chloroformate and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chlorolides,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) 1.3 ml of cyclopentylpropionyl chloride was reacted as in Example 4a) and the product was completed to in each case

1) prednisolone 17- (n-butyl carbonate) -21- (methyl carbonate),

2) prednisolone 17- (n-butyl carbonate) -21- (ethyl carbonate),

3) prednisolone 17- (n-butyl carbonate) -21- (n-propyl carbonate),

4) prednisolone 17- (n-butyl carbonate) -21- (n-butyl carbonate),

5) prednisolone 17- (n-butyl carbonate) -21- (isopropyl carbonate),

6) prednisolone 17- (n-butyl carbonate) -21- (isobutyl carbonate),

7) prednisolone 17- (n-butyl carbonate) -21-acetate,

8) prednisolone 17- (n-butyl carbonate) -21-propionate,

9) prednisolone 17- (n-butyl carbonate) -21-butyrate,

10) prednisolone 17- (n-butyl carbonate) -21-valorate,

11) prednisolone 17- (n-butyl carbonate) -21-cyclopropane carboxylate and

12) Prednisolone 17- (n-butyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of prednisolone 17- (n-butyl carbonate) was reacted with methanesulfonyl chloride as in Example 2f) and completed and crystallized with ether to give prednisolone 17- (n-butyl carbonate) -21-methane sulfonate. Obtained.

If equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride are used instead of methanesulfonyl chloride, the corresponding 17- (n-butyl carbonate) -21-P-toluene sulfonate or prednisolone 17 (n-butyl Carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 제시된 바에 따라 프레드니솔론 및 테트라-(n-부틸)오르토-카보네이트로부터 제조한다.c) Prednisolone di- (n-butyl) orthocarbonate (Rf required primarily for this reaction)

0.6) is prepared from prednisolone and tetra- (n-butyl) ortho-carbonate as set forth in Federal Republic of Germany Patent No. 1,668,079.

0.4)를 제조한다.The first mentioned compound was then hydrolyzed as in Example 1c) to prednisolone 17- (n-butyl carbonate) (Rf

0.4) is prepared.

Example 53

a) 1 g of prednisolone 17 (n-butyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) 1.3 ml of cyclopentylpropionyl chloride were reacted as in Example 4a) and the product was completed to

1) prednisolone 17- (n-butyl carbonate) -21- (methyl carbonate),

2) prednisolone 17- (n-butyl carbonate) -21- (ethyl carbonate),

3) prednisolone 17- (n-butyl carbonate) -21- (n-propyl carbonate),

4) prednisolone 17- (n-butyl carbonate) -21- (n-butyl carbonate),

5) prednisolone 17- (n-butyl carbonate) -21- (isopropyl carbonate),

6) prednisolone 17- (n-butyl carbonate) -21- (isobutyl carbonate),

7) prednisolone 17- (n-butyl carbonate) -21-acetate,

8) prednisolone 17- (n-butyl carbonate) -21-propionate,

9) prednisolone 17- (n-butyl carbonate) -21-butylate,

10) prednisolone 17- (n-butyl carbonate) -21-valorate,

11) prednisolone 17- (n-butyl carbonate) -21-cyclopropanecarboxylate and

12) Prednisolone 17- (n-butyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of prednisolone 17- (n-butyl carbonate) is reacted with methanesulfonyl chloride and completed as in Example 2f) and crystallized with ether to give prednisolone 17- (n-butyl carbonate) -21-methanesulfonate Is obtained.

If equimolar amounts of P-toluene chloride or P-chlorobenzenesulfonyl chloride are used instead of methanesulfonyl chloride, the corresponding prednisolone 17- (n-butyl carbonate) -21-P-toluenesulfonate or prednisolone 17- (n-butyl Carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 제시된 바에 따라 프레드니솔론 및 테트라-(n-부틸)오르토-카보네이트로 부터 제조한다.c) Prednisolone di- (n-butyl) orthocarbonate (Rf required primarily for this reaction)

0.6) are prepared from prednisolone and tetra- (n-butyl) ortho-carbonate as set forth in Federal Republic of Germany Patent No. 1,668,079.

0.4)를 제조한다.The first mentioned compound was then hydrolyzed as in Example 1c) to prednisolone 17- (n-butyl carbonate) (Rf

0.4) is prepared.

Example 54

a) 1 g of cortisone 17- (n-butyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloro-formate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropenecarboxylic acid chloride and

12) 1.3 ml of cyclopentylpropionyl chloride were reacted as in Example 4a) and the product completed to give the corresponding

1) Cortisone 17- (n-butyl carbonate) -21- (methyl carbonate),

2) cortisone 17- (n-butyl carbonate) -21- (ethyl carbonate),

3) cortisone 17- (n-butyl carbonate) -21- (n-propyl carbonate),

4) cortisone 17- (n-butyl carbonate) -21- (n-butyl carbonate),

5) cortisone 17- (n-butyl carbonate) -21- (isopropyl carbonate),

6) cortisone 17- (n-butyl carbonate) -21- (isobutyl carbonate),

7) cortisone 17- (n-butyl carbonate) -21-acetate,

8) cortisone 17- (n-butyl carbonate) -21-propionate,

9) cortisone 17- (n-butyl carbonate) -21-butyrate,

10) cortisone 17- (n-butyl carbonate) -21-valorate,

11) Cortisone 17- (n-butyl carbonate) -21-cyclopropanecarboxylate and

12) Cortisone 17- (n-butyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of Cortisone 17- (n-butyl carbonate) was reacted with methanesulfonyl chloride and treated as in Example 2f) and crystallized with ether to give Cortisone 17- (n-butyl carbonate) -21-methanesulfo Nate is obtained.

If equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride are used instead of methanesulfonyl chloride, the corresponding cortisone 17- (n-butyl carbonate) -21-P-toluenesulfonate or cortisone 17- (n -Butyl carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 제시된 바에 따라 코르티손 및 테트라(n-부틸)오르토 카보네이트로 부터 제조한다. 이어서 처음에 언급된 화합물을 실시예 1c)에서와 같이 가수분해시켜 코르티손 17-(n-부틸 카보네이트)(Rf

0.4)를 얻는다.c) Cortisone di- (n-butyl) orthocarbonate (Rf required primarily for this reaction)

0.6) are prepared from cortisone and tetra (n-butyl) ortho carbonate as set forth in Federal Republic of Germany Patent No. 1,668,079. The initially mentioned compound was then hydrolyzed as in Example 1c) to give Cortisone 17- (n-butyl carbonate) (Rf

0.4).

Example 55

a) 1 g cortisol 17- (n-butyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropanecarboxylic acid chloride,

12) react with 1.3 ml of cyclopentylpropionyl chloride as in Example 4a) and complete the corresponding

1) Cortisol 17- (n-butyl carbonate) -21- (methyl carbonate),

2) cortisol 17- (n-butyl carbonate) -21- (ethyl carbonate),

3) cortisol 17- (n-butyl carbonate) -21- (n-propyl carbonate),

4) cortisol 17- (n-butyl carbonate) -21- (n-butyl carbonate),

5) Cortisol 17- (n-butyl carbonate) -21- (isopropyl carbonate),

6) cortisol 17- (n-butyl carbonate) -21- (isobutyl carbonate),

7) cortisol 17- (n-butyl carbonate) -21-acetate,

8) cortisol 17- (n-butyl carbonate) -21-propionate,

9) cortisol 17- (n-butyl carbonate) -21-butyrate,

10) cortisol 17- (n-butyl carbonate) -21-valorate,

11) Cortisol 17- (n-butyl carbonate) -21-cyclopropane carboxylate and

12) Cortisol 17- (n-butyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of Cortisol 17- (n-butyl carbonate) was reacted with methane sulfonyl chloride and treated as in Example 2f) and then crystallized with ether to give Cortisol 17- (n-butyl carbonate) -21-methane-sulfo Nate is obtained.

If equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride are used instead of methanesulfonyl chloride, the corresponding cortisol 17- (n-butyl carbonate) -21-P-toluenesulfonate or cortisol 17- (n -Butyl carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)는 독일연방공화국 특허 제1,668,079호에 제시된 바에 따라 코르티솔 및 테트라-(n-부틸)오르토 카보네이트로 부터 제조된다.c) Cortisol di- (n-butyl) orthocarbonate (Rf required for the reaction)

0.6) are prepared from cortisol and tetra- (n-butyl) ortho carbonate as set forth in Federal Republic of Germany Patent No. 1,668,079.

0.4)가 얻어진다.The first mentioned compound was then hydrolyzed as in Example 1c) to form Cortisol 17- (n-butyl carbonate) (Rf

0.4) is obtained.

Example 56

a) 1 g of beclomethasone 17- (n-butyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride and

12) react with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete and

1) beclomethasone 17- (n-butyl carbonate) -21- (methyl carbonate),

2) beclomethasone 17- (n-butyl carbonate) -21- (ethyl carbonate),

3) beclomethasone 17- (n-butyl carbonate) -21- (n-propyl carbonate),

4) beclomethasone 17- (n-butyl carbonate) -21- (n-butyl carbonate),

5) beclomethasone 17- (n-butyl carbonate) -21- (isopropyl carbonate),

6) beclomethasone 17- (n-butyl carbonate) -21- (isobutyl carbonate),

7) beclomethasone 17- (n-butyl carbonate) -21-acetate,

8) beclomethasone 17- (n-butyl carbonate) -21-propionate,

9) beclomethasone 17- (n-butyl carbonate) -21-butyrate,

10) beclomethasone 17- (n-butyl carbonate) -21-valorate,

11) beclomethasone 17- (n-butyl carbonate) -21-cyclopropanecarboxylate and

12) Beclomethasone 17- (n-butyl carbonate) -21-cyclopentyl propionate is obtained.

Example 57

a) 1 g of 6α-fluorodexamethasone 17- (n-butyl carbonate) is reacted with methyl chloroformate and instead of

1) 0.8 ml of chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) react with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete to yield

1) 6α-fluorodexamethasone 17- (n-butyl carbonate) -21- (methyl carbonate),

2) 6α-fluorodexamethasone 17- (n-butyl carbonate)-(ethyl carbonate),

3) 6α-fluorodexamethasone 17- (n-butyl carbonate) -21- (n-propyl carbonate),

4) 6α-fluorodexamethasone 17- (n-butyl carbonate) -21- (n-butyl carbonate),

5) 6α-fluorodexamethasone 17- (n-butyl carbonate) -21- (isopropyl carbonate),

6) 6α-fluorodexamethasone 17- (n-butyl carbonate) -21- (isobutyl carbonate),

7) 6α-fluorodexamethasone 17- (n-butyl carbonate) -21-acetate,

8) 6α-fluorodexamethasone 17- (n-butyl carbonate) -21-propionate,

9) 6α-fluorodexamethasone 17- (n-butyl carbonate) -21-butyrate,

10) 6α-fluorodexamethasone 17- (n-butyl carbonate) -21-valorate,

11) 6α-fluorodexamethasone 17- (n-butyl carbonate) -21-cyclopropanecarboxylate,

12) 6α-fluorodexamethasone 17- (n-butyl carbonate) -21-cyclopentyl propionate is obtained respectively.

b) 3 g of 6α-fluorodexamethasone 17- (n-butyl carbonate) is reacted with methanesulfonyl chloride as in Example 2f) and finished and crystallized with ether to give 6α-fluorodexamemethasone 17- (n-butyl carbonate). ) -21-methane sulfonate is obtained.

If equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride are used instead of methanesulfonyl chloride, the corresponding 6α-fluorodexamemethasone 17- (n-butyl carbonate) -21-P-toluenesulfonate or 6α -Fluorodexamethason 17- (n-butyl carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)는 독일연방공화국 특허제1,668,079호에 전시된 바에 따라 6α-플루오로 덱사메타손 및 테트라-(n-부틸)오르토 카보네이트로 부터 제조된다. 이어서, 처음에 언급된 화합물을 실시예 1c)에서와 같이 가수분해하여 6α-플루오로덱사메타손 17-(n-부틸 카보네이트)(Rf

0.4)를 얻는다.c) 6α-fluorodexamethasone di- (n-butyl) orthocarbonate (Rf

0.6) is prepared from 6α-fluoro dexamethasone and tetra- (n-butyl) ortho carbonate as exhibited in Federal Republic of Germany Patent No. 1,668,079. Subsequently, the first mentioned compound was hydrolyzed as in Example 1c) to give 6α-fluorodexamemethasone 17- (n-butyl carbonate) (Rf

0.4).

Example 58

a) instead of reacting 1 g of betamethasone 17- (n-butyl carbonate) with methyl chloroformate,

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of methyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) react with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete to yield

1) betamethasone 17- (n-butyl carbonate) -21- (methyl carbonate),

2) betamethasone 17- (n-butyl carbonate) -21- (ethyl carbonate),

3) betamethasone 17- (n-butyl carbonate) -21- (n-propyl carbonate),

4) betamethasone 17- (n-butyl carbonate) -21- (n-butyl carbonate),

5) betamethasone 17- (n-butyl carbonate) -21- (isopropyl carbonate),

6) betamethasone 17- (n-butyl carbonate) -21- (isobutyl carbonate),

7) betamethasone 17- (n-butyl carbonate) -21-acetate,

8) betamethasone 17- (n-butyl carbonate) -21-propionate,

9) betamethasone 17- (n-butyl carbonate) -21-butyrate,

10) betamethasone 17- (n-butyl carbonate) -21-valorate,

11) betamethasone 17- (n-butyl carbonate) -21-cyclopropanecarboxylate,

12) Betamethasone 17- (n-butyl carbonate) -21-cyclopentyl propionate is obtained respectively.

b) 3 g of betamethasone 17- (n-butyl carbonate) is reacted with methanesulfonyl chloride as in Example 2f) and the product is crystallized with ether to give betamethasone 17- (n-butyl carbonate) -21-methane sulfo Nate is obtained.

If equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride are used instead of methanesulfonyl chloride, the corresponding betamethasone 17- (n-butyl carbonate) -21-P-toluenesulfonate or betamethasone 17- (n -Butyl carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)는 독일연방공화국 특허제1,668,079호에 제시된 바에 따라 베타메타손 및 테트라-(n-부틸)오르토 카보네이트로부터 제조한다. 이어서, 처음에 언급된 화합물을 실시예 1c)에서와 같이 가수분해하여 베타메타손 17-(n-부틸 카보네이트)(Rf

0.4)를 얻는다.c) betamethasone di- (n-butyl) orthocarbonate (Rf

0.6) is prepared from betamethasone and tetra- (n-butyl) ortho carbonate as set forth in Federal Republic of Germany Patent No. 1,668,079. Subsequently, the first mentioned compound was hydrolyzed as in Example 1c) to betamethasone 17- (n-butyl carbonate) (Rf

0.4).

Example 59

a) instead of reacting 1 g of 6α-fluoroprednisolone 17- (n-butyl carbonate) with methyl chloroformate,

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) react with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete to yield

1) 6α-fluoroprednisolone 17- (n-butyl carbonate) -21- (methyl carbonate),

2) 6α-fluoroprednisolone 17- (n-butyl carbonate) -21- (ethyl carbonate),

3) 6α-fluoroprednisolone 17- (n-butyl carbonate) -21- (n-propyl carbonate),

4) 6α-fluoroprednisolone 17- (n-butyl carbonate) -21- (n-butyl carbonate),

5) 6α-fluoroprednisolone 17- (n-butyl carbonate) -21- (isopropyl carbonate),

6) 6α-fluoroprednisolone 17- (n-butyl carbonate) -21- (isobutyl carbonate),

7) 6α-fluoroprednisolone 17- (n-butyl carbonate) -21-acetate,

8) 6α-fluoroprednisolone 17- (n-butyl carbonate) -21-propionate,

9) 6α-fluoroprednisolone 17- (n-butyl carbonate) -21-butyrate,

10) 6α-fluoroprednisolone 17- (n-butyl carbonate) -21-valorate,

11) 6α-fluoroprednisolone 17- (n-butyl carbonate) -21-cyclopropanecarboxylate,

12) 6α-fluoroprednisolone 17- (n-butyl carbonate) -21-cyclopentyl propionate is obtained respectively.

b) 3 g of 6α-fluoroprednisolone 17- (n-butyl carbonate) is reacted with methanesulfonyl chloride and treated as in Example 2f) to crystallize with ether to give 6α-fluoroprednisolone 17- (n-butyl carbonate ) -21-methane sulfonate is obtained.

If equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride are used instead of methanesulfonyl chloride, the corresponding 6α-fluoroprednisolone 17- (n-butyl carbonate) -21-P-toluenesulfonate or 6α -Fluoroprednisolone 17- (n-butyl carbonate) -21-P-chloro benzenesulfonate is obtained.

0.4)가 얻어진다.Subsequently, the first mentioned compound was hydrolyzed as in Example (c) to give 6α-fluoropredonisolone (7- (n-butylcarbonate) (RF

0.4) is obtained.

0.6)은 독일연방공화국 특허제1,668,079호에 제시된 바에따라 6α-플루오로프레드니솔론 및 테트라-(n-부틸)오르토 카보네이트로부터 제조한다. 이어서, 처음에 언급된 화합물을 실시예 1c)에서와 같이 가수분해시켜 6α-플루오로프레드니솔론 17-(n-부틸 카보네이트)(Rf

0.4)를 얻는다.c) 6α-fluoroprednisolone di- (n-butyl) orthocarbonate (Rf

0.6) is prepared from 6α-fluoroprednisolone and tetra- (n-butyl) ortho carbonate as set forth in Federal Republic of Germany Patent No. 1,668,079. Subsequently, the first mentioned compound was hydrolyzed as in Example 1c) to give 6α-fluoroprednisolone 17- (n-butyl carbonate) (Rf

0.4).

Example 60

a) 1 g of 16α- or β-methyl-prednisolone 17- (n-butyl carbonate) instead of reacting with methyl chloroformate, respectively

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) react with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete to yield

1) 16α- or β-methyl-prednisolone 17- (n-butyl carbonate) -21- (methyl carbonate),

2) 16α- or β-methyl-prednisolone 17- (n-butyl carbonate) -21- (ethyl carbonate),

3) 16α- or β-methyl-prednisolone 17- (n-butyl carbonate) -21- (n-propyl carbonate),

4) 16α- or β-methyl-prednisolone 17- (n-butyl carbonate) -21- (n-butyl carbonate),

5) 16α- or β-methyl-prednisolone 17- (n-butyl carbonate) -21- (isopropyl carbonate),

6) 16α- or β-methyl-prednisolone 17- (n-butyl carbonate) -21- (isobutyl carbonate),

7) 16α- or β-methyl-prednisolone 17- (n-butyl carbonate) -21-acetate,

8) 16α- or β-methyl-prednisolone 17- (n-butyl carbonate) -21-propionate,

9) 16α- or β-methyl-prednisolone 17- (n-butyl carbonate)

10) 16α- or β-methyl-prednisolone 17- (n-butyl carbonate) -21-valorate,

11) 16α- or β-methyl-prednisolone 17- (n-butyl carbonate) -21-cyclopropanecarboxylate,

12) 16α- or β-methyl-prednisolone 17- (n-butyl carbonate) -21-cyclopentyl propionate are obtained respectively.

b) 3 g of 16α- or β-methyl-prednisolone 17- (n-butyl carbonate) is reacted with methanesulfonyl chloride as in Example 2f) and the product is crystallized with ether to give 16α- or β-methyl- Prednisolone 17- (n-butyl carbonate) -21-methane sulfonate is obtained. If equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride are used instead of methanesulfonyl chloride, the corresponding 16α- or β-methyl-prednisolone 17- (n-butyl carbonate) -21-P-toluenesulfo Nate or 16α- or β-methyl-prednisolone 17- (n-butyl carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)은 독일연방공화국 특허 제1,668,079호에 제시된 바에 따라 16α-또는 β-메틸-프레드니솔론 및 테트라-(n-부틸)오르토 카보네이트로부터 제조된다. 이어서, 처음에 언급된 화합물을 실시예 c)에서와 같이 가수분해하여 16α-또는 β-메틸-프레드니솔론 17-(n-부틸 카보네이트)를 얻는다.c) 16α- or β-methyl-prednisolone di- (n-butyl) orthocarbonate (Rf

0.6) are prepared from 16α- or β-methyl-prednisolone and tetra- (n-butyl) ortho carbonate as set forth in Federal Republic of Germany Patent No. 1,668,079. The compound mentioned initially is then hydrolyzed as in example c) to give 16α- or β-methyl-prednisolone 17- (n-butyl carbonate).

Example 61

a) 1 g of 6α, 16α- or β-dimethyl-prednisolone 17- (n-butyl carbonate) instead of reacting with methyl chloroformate, respectively

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) 1.3 ml of cyclopentyl propionyl chloride were reacted and finished as in Example 4a) to give the corresponding

1) 6α, 16α- or β-dimethyl-prednisolone 17- (n-butyl carbonate) -21- (methyl carbonate),

2) 6α, 16α- or β-dimethyl-prednisolone 17- (n-butyl carbonate) -21- (ethyl carbonate),

3) 6α, 16α- or β-dimethyl-prednisolone 17- (n-butyl carbonate) -21- (n-propyl carbonate),

4) 6α, 16α- or β-dimethyl-prednisolone 17- (n-butyl carbonate) -21- (n-butyl carbonate),

5) 6α, 16α- or β-dimethyl-prednisolone 17- (n-butyl carbonate) -21- (isopropyl carbonate),

6) 6α, 16α- or β-dimethyl-prednisolone 17- (n-butyl carbonate) -21- (isobutyl carbonate),

7) 6α, 16α- or β-dimethyl-prednisolone 17- (n-butyl carbonate) -21-acetate,

8) 6α, 16α- or β-dimethyl-prednisolone 17- (n-butyl carbonate) -21-propionate,

9) 6α, 16α- or β-dimethyl-prednisolone 17- (n-butyl carbonate) -21-butyrate,

10) 6α, 16α- or β-dimethyl-prednisolone 17- (n-butyl carbonate) -21-valorate,

11) 6α, 16α- or β-dimethyl-prednisolone 17- (n-butyl carbonate) -21-cyclopropanecarboxylate,

12) 6α, 16α- or β-dimethyl-prednisolone 17- (n-butyl carbonate) -21-cyclopentylpropionate are obtained respectively.

b) 3 g of 6α, 16α- or β-dimethyl-prednisolone 17- (n-butyl carbonate) is reacted with methanesulfonyl chloride as in Example 2f) and the product is crystallized with ether to give 6α, 16α-or β-dimethyl-prednisolone 17- (n-butyl carbonate) -21-methane sulfonate is obtained. If equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride are used instead of methanesulfonyl chloride, the corresponding 6α, 16α- or β-dimethyl-prednisolone 17- (n-butyl carbonate) -21-P- Toluenesulfonate or 6α, 16α- or β-dimethyl-prednisolone 17- (n-butyl carbonate) -21-P-chloro-benzenesulfonate is obtained.

0.6)은 독일연방공화국 특허제1,668,079호에 제시된 바에 따라 6α, 16α-또는 β-디메틸-프레드니솔론 및 테트라-(n-부틸)오르토 카보네이트로부터 얻어진다. 이어서, 처음에 언급된 화합물을 실시예 1c에서와 같이 가수분해하여 6α, 16α-또는 β-디메틸-프레드니솔론 17-(n-부틸 카보네이트)(Rf

0.4)를 얻는다.c) 6α, 16α- or β-dimethyl-prednisolone di- (n-butyl) orthocarbonate (Rf

0.6) is obtained from 6α, 16α- or β-dimethyl-prednisolone and tetra- (n-butyl) ortho carbonate as set forth in Federal Republic of Germany Patent No. 1,668,079. Subsequently, the first mentioned compound was hydrolyzed as in Example 1c to give 6α, 16α- or β-dimethyl-prednisolone 17- (n-butyl carbonate) (Rf

0.4).

Example 62

a) 1 g of 9α-chloro-16α-methyl-prednisolone 17- (n-butyl carbonate) in place of methyl chloroformate, respectively

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) react with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete to yield

1) 9α-chloro-16α-methyl-prednisolone 17- (n-butyl carbonate) -21- (methyl carbonate),

2) 9α-chloro-16α-methyl-prednisolone 17- (n-butyl carbonate) -21- (ethyl carbonate),

3) 9α-chloro-16α-methyl-prednisolone 17- (n-butyl carbonate) -21- (n-propyl carbonate),

4) 9α-chloro-16α-methyl-prednisolone 17- (n-butyl carbonate) -21- (n-butyl carbonate),

5) 9α-chloro-16α-methyl-prednisolone 17- (n-butyl carbonate) -21- (isopropyl carbonate),

6) 9α-chloro-16α-methyl-prednisolone 17- (n-butyl carbonate) -21- (isobutyl carbonate),

7) 9α-chloro-16α-methyl-prednisolone 17- (n-butyl carbonate) -21-acetate,

8) 9α-chloro-16α-methyl-prednisolone 17- (n-butyl carbonate) -21-propionate,

9) 9α-chloro-16α-methyl-prednisolone 17- (n-butyl carbonate) -21-butyrate,

10) 9α-chloro-16α-methyl-prednisolone 17- (n-butyl carbonate) -21-valorate,

11) 9α-chloro-16α-methyl-prednisolone 17- (n-butyl carbonate) -21-cyclopropane carboxylate,

12) 9α-chloro-16α-methyl-prednisolone 17- (n-butyl carbonate) -21-cyclopentyl propionate is obtained respectively.

b) 3 g of 9α-chloro-16α-methyl-prednisolone 17- (n-butyl carbonate) was reacted with methanesulfonyl chloride as in Example 2f) and the product was completed and crystallized with ether to give 9α-chloro-16α- Methyl-prednisolone 17- (n-butyl carbonate) -21-methane sulfonate is obtained.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methanesulfonyl chloride results in the corresponding 9α-chloro-16α-methyl-prednisolone 17- (n-butyl carbonate) 21-P-toluenesulfo Nate or 9α-chloro-16α-methyl-prednisolone 17- (n-butyl carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)은 독일연방공화국 특허제1,668,079호에 제시된 바에 따라 9α-클로로-16α-메틸-프레드니솔론 및 테트라-(n-부틸)오르토 카보네이트로부터 제조한다. 이어서, 처음에 언급된 화합물을 실시예 1c)에서와 같이 가수분해시키면 9α-클로로-16α-메틸-프레드니솔론 17-(n-부틸 카보네이트)(Rf

0.4)가 얻어진다.c) 9α-chloro-16α-methyl-prednisolone di- (n-butyl) orthocarbonate (Rf

0.6) is prepared from 9α-chloro-16α-methyl-prednisolone and tetra- (n-butyl) ortho carbonate as set forth in Federal Republic of Germany Patent No. 1,668,079. Subsequently, the first mentioned compound was hydrolyzed as in Example 1c) to give 9α-chloro-16α-methyl-prednisolone 17- (n-butyl carbonate) (Rf

0.4) is obtained.

Example 63

a) 1 g of 9α-chloro-prednisolone 17- (n-butyl carbonate) in place of methyl chloroformate, respectively

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) react with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete to yield

1) 9α-chloro-prednisolone 17- (n-butyl carbonate) -21- (methyl carbonate),

2) 9α-chloro-prednisolone 17- (n-butyl carbonate) -21- (ethyl carbonate),

3) 9α-chloro-prednisolone 17- (n-butyl carbonate) -21- (n-propyl carbonate),

4) 9α-chloro-prednisolone 17- (n-butyl carbonate) -21- (n-butyl carbonate),

5) 9α-chloro-prednisolone 17- (n-butyl carbonate) -21- (isopropyl carbonate),

6) 9α-chloro-prednisolone 17- (n-butyl carbonate) -21- (isobutyl carbonate),

7) 9α-chloro-prednisolone 17- (n-butyl carbonate) -21-acetate,

8) 9α-chloro-prednisolone 17- (n-butyl carbonate) -21-propionate,

9) 9α-chloro-prednisolone 17- (n-butyl carbonate) -21-butyrate,

10) 9α-chloro-prednisolone 17- (n-butyl carbonate) -21-valorate,

11) 9α-chloro-prednisolone 17- (n-butyl carbonate) -21-cyclopropane carboxylate,

12) 9α-chloro-prednisolone 17- (n-butyl carbonate) -21-cyclopentyl propionate is obtained respectively.

b) 3 g of 9α-chloro-prednisolone 17- (n-butyl carbonate) was reacted with methanesulfonyl chloride as in Example 2f) and the product was completed and crystallized with ether to give 9α-chloro-prednisolone 17- (n- Butyl carbonate) -21-methane sulfonate is obtained.

If equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride are used instead of methanesulfonyl chloride, the corresponding 9α-chloro-prednisolone 17- (n-butyl carbonate) -21-P-toluenesulfonate or 9α Chloro-prednisolone 17- (n-butyl carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)은 독일연방공화국 특허 제1,668,079호에 제시된 바에 따라 9α-클로로-프레드니솔론 및 테트라-(n-부틸)요르토 카보네이트로 부터 얻어진다.c) 9α-chloro-prednisolone di- (n-butyl) -ortho carbonate (Rf

0.6) are obtained from 9α-chloro-prednisolone and tetra- (n-butyl) yrto carbonate as set forth in Federal Republic of Germany Patent No. 1,668,079.

0.4)를 얻는다.The first mentioned compound was then hydrolyzed as in Example 1c) to give 9α-chloro-prednisolone 17- (n-butyl carbonate) (Rf

0.4).

Example 64

a) 1 g of prednisolone 17- (n-pentylcarbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) react with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete to yield

1) prednisolone 17- (n-pentyl carbonate) -21-methyl carbonate,

2) prednisolone 17- (n-pentyl carbonate) -21-ethyl carbonate,

3) prednisolone 17- (n-pentyl carbonate) -21- (n-propyl carbonate),

4) prednisolone 17- (n-pentyl carbonate) -21- (n-butyl carbonate),

5) prednisolone 17- (n-pentyl carbonate) -21- (isopropyl carbonate),

6) prednisolone 17- (n-pentyl carbonate) -21- (isobutyl carbonate),

7) prednisolone 17- (n-pentyl carbonate) -21-acetate,

8) prednisolone 17- (n-pentyl carbonate) -21-propionate,

9) prednisolone 17- (n-pentyl carbonate) -21-butyrate,

10) prednisolone 17- (n-pentyl carbonate) -21-valorate,

11) prednisolone 17- (n-pentyl carbonate) -21-cyclopropanecarboxylate,

12) Prednisolone 17- (n-pentyl carbonate) -21-cyclopentyl propionate is obtained respectively.

b) Reacting 3 g of prednisolone 17- (n-pentyl carbonate) with methane sulfonyl chloride as in Example 2f) and completing the product to crystallize with ether gives prednisolone 17- (n-butyl carbonate) -21-methane sulfo Nate is obtained. Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methanesulfonyl chloride results in the corresponding prednisolone 17- (n-pentyl carbonate) 21-P-toluenesulfonate or prednisolone 17- (n- Pentyl carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)은 독일연방공화국 특허제1,668,079호에 제시된 바에 따라 프레드니솔론 및 테트라-(n-펜틸)오르토 카보네이트로 부터 제조하고 이어서, 처음에 언급된 화합물을 실시예 1c)에서와 같이 가수분해 하여 프레드니솔론 17-(n-펜틸카보네이트)(Rf

0.4)를 얻는다.c) prednisolone di- (n-pentyl) orthocarbonate (Rf

0.6) is prepared from prednisolone and tetra- (n-pentyl) ortho carbonate as set forth in Federal Republic of Germany Patent No. 1,668,079, and then hydrolyzed as described in Example 1c) to prednisolone 17- (n-pentylcarbonate) (Rf

0.4).

Example 65

a) 1 g of prednisolone 17- (n-pentylcarbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) react with 1.3 ml of cyclopentyl propionyl chloride as in Example 4a) and complete to yield

1) prednisolone 17- (n-pentyl carbonate) -21- (methyl carbonate),

2) prednisolone 17- (n-pentyl carbonate) -21- (ethyl carbonate),

3) prednisolone 17- (n-pentyl carbonate) -21- (propyl carbonate),

4) prednisolone 17- (n-pentyl carbonate) -21- (n-butyl carbonate),

5) prednisolone 17- (n-pentyl carbonate) -21- (isopropyl carbonate),

6) prednisolone 17- (n-pentyl carbonate) -21- (isobutyl carbonate),

7) prednisolone 17- (n-pentyl carbonate) -21-acetate,

8) prednisolone 17- (n-pentyl carbonate) -21-propionate,

9) prednisolone 17- (n-pentyl carbonate) -21-butyrate,

10) prednisolone 17- (n-pentyl carbonate) -21-valorate,

11) prednisolone 17- (n-pentyl carbonate) -21-cyclopropane carboxylate,

12) Prednisolone 17- (n-pentyl carbonate) -21-cyclopentylpropionate is obtained respectively.

b) Reacting 3 g of prednisolone 17- (n-pentyl carbonate) with methane sulfonylchloride as in Example 2f) and completing the product to crystallize with ether gives prednisolone 17- (n-pentyl carbonate) -21-methane sulfo Nate is obtained.

Use of equimolar amounts of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methanesulfonyl chloride affords the corresponding prednisolone 17- (n-pentyl carbonate) -21-P-chloro benzenesulfonate.

0.6)은 독일연방공화국 특허 제1,668,079호에 제시된 바에 따라 프레드니솔론 및 테트라-(n-펜틸)오르토 카보네이트로부터 제조하고 이어서, 처음에 언급된 화합물을 실시예 1c)에서와 같이 처리하여 프레드니솔론 17-(n-펜틸카보네이트)(Rf

0.4)를 얻는다.c) prednisolone di- (n-pentyl) orthocarbonate (Rf

0.6) is prepared from prednisolone and tetra- (n-pentyl) ortho carbonate as set forth in Federal Republic of Germany Patent No. 1,668,079, and then the first mentioned compound is treated as in Example 1c) to prednisolone 17- (n Pentylcarbonate) (Rf

0.4).

Example 66

a) 1 g cortisone 17- (n-pentylcarbonate) instead of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) Reaction and completion in the same manner as in Example 4a with 1.3 ml of cyclopentyl propionyl chloride resulted in a corresponding

1) Cortisone 17- (n-pentyl carbonate) -21- (methyl carbonate),

2) cortisone 17- (n-pentyl carbonate) -21- (ethyl carbonate),

3) cortisone 17- (n-pentyl carbonate) -21- (n-propyl carbonate),

4) cortisone 17- (n-pentyl carbonate) -21- (n-butyl carbonate),

5) cortisone 17- (n-pentyl carbonate) -21- (isopropyl carbonate),

6) cortisone 17- (n-pentyl carbonate) -21- (isobutyl carbonate),

7) cortisone 17- (n-pentyl carbonate) -21-acetate,

8) cortisone 17- (n-pentyl carbonate) -21-propionate,

9) cortisone 17- (n-pentyl carbonate) -21-butyrate,

10) cortisone 17- (n-pentyl carbonate) -21-valorate,

11) Cortisone 17- (n-pentyl carbonate) -21-cyclopropanecarboxylate and

12) Cortisone 17- (n-pentyl carbonate) -21-cyclopentylpropionate is obtained respectively.

b) 3 g of Cortisone 17- (n-pentyl carbonate) is reacted with methanesulfonyl chloride in the same manner as in Example 2f), and the product is completed and crystallized from ether to give Cortisone 17- (n-pentyl carbonate) -21- Methane sulfonate is obtained.

If equimolar amounts of P-toluene sulfonyl chloride or P-chloro benzenesulfonyl chloride are used in place of methanesulfonyl chloride, the corresponding cortisone 17- (n-pentyl carbonate) -21-P-toluenesulfonate or cortisone 17- ( n-pentyl carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)은 독일연방공화국 특허제1,668,079호에 제시된 바에 따라 코르티손과 테트라-(n-펜틸)오르토 카보네이트로 부터 제조한다.c) Cortisone di- (n-pentyl) orthocarbonate (Rf

0.6) is prepared from cortisone and tetra- (n-pentyl) ortho carbonate as set forth in Federal Republic of Germany Patent No. 1,668,079.

0.4)가 얻어진다.The first mentioned compound was then hydrolyzed as in Example 1c) to give Cortisone 17- (n-pentyl carbonate) (Rf

0.4) is obtained.

Example 67

a) 1 g of cortisone 17- (n-pentyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) Reaction and completion in the same manner as in Example 4a) with 1.3 ml of cyclopentylpropyl chloride corresponding to each case

1) Cortisol 17- (n-pentyl carbonate) -21- (methyl carbonate),

2) cortisol 17- (n-pentyl carbonate) -21- (ethyl carbonate),

3) cortisol 17- (n-pentyl carbonate) -21- (n-propyl carbonate),

4) cortisol 17- (n-pentyl carbonate) -21- (n-butyl carbonate),

5) Cortisol 17- (n-pentyl carbonate) -21- (isopropyl carbonate),

6) cortisol 17- (n-pentyl carbonate) -21- (isobutyl carbonate),

7) Cortisol 17- (n-pentyl carbonate) -21-acetate,

8) cortisol 17- (n-pentyl carbonate) -21-propionate,

9) cortisol 17- (n-pentyl carbonate) -21-butyrate,

10) cortisol 17- (n-pentyl carbonate) -21-valorate,

11) Cortisol 17- (n-pentyl carbonate) -21-cyclopropane carboxylate,

12) Cortisol 17- (n-pentyl carbonate) -21-cyclopentyl propionate is obtained respectively.

b) 3 g of Cortisol 17- (n-pentyl carbonate) is reacted with methanesulfonyl chloride in the same manner as in Example 2f), and the product is completed and crystallized from ether to give Cortisol 17- (n-pentyl carbonate) -21- Methane sulfonate is obtained.

If equivalent moles of P-toluene sulfonyl chloride or P-chloro benzenesulfonyl chloride are used in place of methanesulfonyl chloride, the corresponding cortisol 17- (n-pentyl carbonate) -21-P-toluenesulfonate or cortisol 17- (n-pentyl carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)은 독일연방공화국 특허 제1,668,079호에 제시된 바와같이 코르티솔과 테트라-(n-펜틸)오르토 카보네이트로 부터 제조한다. 이어서 처음 언급한 화합물을 실시예 1c)에서와 같은 방법으로 가수분해시켜 코르티솔 17-(n-펜틸 카보네이트)(Rf

0.4)를 얻는다.Cortisol di- (n-pentyl) orthocarbonate (Rf) first used in the reaction

0.6) is prepared from cortisol and tetra- (n-pentyl) ortho carbonate, as shown in Federal Republic of Germany Patent No. 1,668,079. The first mentioned compound was then hydrolyzed in the same manner as in Example 1c) to form Cortisol 17- (n-pentyl carbonate) (Rf

0.4).

Example 68

a) 1 g of beclomethasone 17- (n-pentylcarbonate) instead of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of n-pentyl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) react with 1.3 ml of cyclopentylpropionyl chloride in the same manner as in Example 4a) and complete

1) beclomethasone 17- (n-pentyl carbonate) -21- (methyl carbonate),

2) beclomethasone 17- (n-pentyl carbonate) -21- (ethyl carbonate),

3) beclomethasone 17- (n-pentyl carbonate) -21- (n-propyl carbonate),

4) beclomethasone 17- (n-pentyl carbonate) -21- (n-butyl carbonate),

5) beclomethasone 17- (n-pentyl carbonate) -21- (isopropyl carbonate),

6) beclomethasone 17- (n-pentyl carbonate) -21- (isobutyl carbonate),

7) beclomethasone 17- (n-pentyl carbonate) -21-acetate,

8) beclomethasone 17- (n-pentyl carbonate) -21-propionate,

9) beclomethasone 17- (n-pentyl carbonate) -21-butyrate,

10) beclomethasone 17- (n-pentyl carbonate) -21-valorate,

11) beclomethasone 17- (n-pentyl carbonate) -21-cyclopropane carboxylate,

12) Beclomethasone 17- (n-pentyl carbonate) -21-cyclopentyl is obtained respectively.

b) When 3 g of beclomethasone 17- (n-pentylcarbonate) is reacted with methanesulfonyl chloride in the same manner as in Example 2f), and the product is completed and crystallized in ether, beclomethasone 17- (n-pentylcarbonate) is obtained. Carbonate) -21-methanesulfonate is obtained.

If you use the same moles of P-toluenesulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methanesulfonyl chloride, the corresponding beclomethasone 17- (n-pentyl carbonate) -21-P-toluenesulfonate or Beck Lomethasone 17- (n-pentyl carbonate) -21-P-chlorobenzene sulfonate is obtained.

0.6)은 독일연방공화국 특허 제1,668,079호에 제시된 바에 따라 베크로메타손과 테트라-(n-펜틸)오르토 카보네이트로부터 제조한다.c) di- (n-pentyl) ortho carbonate (Rf required for the first time in the reaction)

0.6) is prepared from beclomethasone and tetra- (n-pentyl) ortho carbonate as set forth in Federal Republic of Germany Patent No. 1,668,079.

0.4)를 얻는다.The first mentioned compound was then hydrolyzed to give 17- (n-pentylcarbonate) (Rf

0.4).

Example 69

a) 1 g of 6α-fluorodexamethasone 17- (n-pentylcarbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) After reacting and completing 1.3 ml of cyclopentylpropionyl chloride as in Example 4a),

1) 6α-fluorodexamethasone 17- (n-pentyl carbonate) -21- (methyl carbonate),

2) 6α-fluorodexamethasone 17- (n-pentyl carbonate) -21- (ethyl carbonate),

3) 6α-fluorodexamemethasone 17- (n-pentyl carbonate) -21- (n-propyl carbonate),

4) 6α-fluorodexamemethasone 17- (n-pentyl carbonate) -21- (n-butyl carbonate),

5) 6α-fluorodexamemethasone 17- (n-pentyl carbonate) -21- (isopropyl carbonate),

6) 6α-fluorodexamethasone 17- (n-pentyl carbonate) -21- (isobutyl carbonate),

7) 6α-fluorodexamemethasone 17- (n-pentyl carbonate) -21-acetate,

8) 6α-fluorodexamethasone 17- (n-pentyl carbonate) -21-propionate,

9) 6α-fluorodexamethasone 17- (n-pentyl carbonate) -21-butyrate,

10) 6α-fluorodexamethasone 17- (n-pentyl carbonate) -21-valorate,

11) 6α-fluorodexamemethasone 17- (n-pentyl carbonate) -21-cyclopropanecarboxylate,

12) 6α-fluorodexamemethasone 17- (n-pentyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 6α-fluorodexamethasone 17- (n-pentyl carbonate) was reacted with methanesulfonyl chloride in the same manner as in Example 2f), and the product was completed and crystallized with ether to give 6α-fluorodexamethason 17- (n -Pentyl carbonate) -21-p-methanesulfonate is obtained.

If the same moles of P-toluenesulfonyl chloride or P-chlorobenzenesulfonyl chloride are used instead of methane sulfonyl chloride, the corresponding 6α-fluorodexamemethasone 17- (n-pentyl carbonate) -21-P-toluenesulfonate Or 6α-fluorodexamethasone 17- (n-pentyl carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)은 독일연방공화국 특허 제1,668,079호에 제시된 바에 따라 6α-플루오로덱사메타손과 테트라-(n-펜틸)오르토카보네이트로부터 제조한다. 이어서 처음으로 언급한 화합물을 실시예 1c)에서와 같이 가수분해하여 6α-플루오로덱사메타손 17-(n-펜틸 카보네이트)(Rf

0.4)를 제조한다.c) 6α-fluorodexamemethasone 17- (n-pentylortho carbonate) (Rf first used in the reaction)

0.6) is prepared from 6α-fluorodexamemethasone and tetra- (n-pentyl) orthocarbonate as set forth in Federal Republic of Germany Patent No. 1,668,079. The first mentioned compound was then hydrolyzed as in Example 1c) to give 6α-fluorodexamemethasone 17- (n-pentyl carbonate) (Rf

0.4) is prepared.

Example 70

a) 1 g of betamethasone 17- (n-pentyl carbonate) in place of methylchloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopenta carboxylic acid chloride,

12) React with 1.3 ml of cyclopentylpropionyl chloride in the same manner as in Example 4a) and complete the corresponding

1) betamethasone 17- (n-pentyl carbonate) -21- (methyl carbonate),

2) betamethasone 17- (n-pentyl carbonate) -21- (ethyl carbonate),

3) betamethasone 17- (n-pentyl carbonate) -21- (n-propyl carbonate),

4) betamethasone 17- (n-pentyl carbonate) -21- (n-butyl carbonate),

5) betamethasone 17- (n-pentyl carbonate) -21- (isopropylcarbonate),

6) betamethasone 17- (n-pentyl carbonate) -21- (isobutyl carbonate),

7) betamethasone 17- (n-pentyl carbonate) -21- (acetate),

8) betamethasone 17- (n-pentyl carbonate) -21-propionate,

9) betamethasone 17- (n-pentyl carbonate) -21-butyrate,

10) betamethasone 17- (n-pentyl carbonate) -21-valorate,

11) betamethasone 17- (n-pentyl carbonate) -21-cyclopropane carboxylate,

12) Betamethasone 17- (n-pentyl carbonate) -21-cyclopentyl propionate is obtained respectively.

b) 3 g of betamethasone 17- (n-pentyl carbonate) was reacted with methanesulfonyl chloride in the same manner as in Example 2f), and the product was completed and crystallized in ether to betamethasone 17- (n-pentyl carbonate) -21-methane. Sulfonate is obtained.

Using the same moles of P-toluenesulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methanesulfonyl chloride, 17- (n-pentyl carbonate) -21-P-toluenesulfonate or betamethasone 17- (n-pentyl Carbonate) -21-P-chloro benzenesulfonate is obtained respectively.

0.6)은 독일연방공화국 특허 제1,668,079호에 제시된 바에 따라 베타메타손과 테트라-(n-펜틸)오르토 카보네이트로부터 제조한다.c) di- (n-pentyl) ortho carbonate (Rf required for the first time in the reaction)

0.6) is prepared from betamethasone and tetra- (n-pentyl) ortho carbonate as set forth in Federal Republic of Germany Patent No. 1,668,079.

Next, the first-mentioned compound is hydrolyzed in the same manner as in Example 1c) to obtain betamethasone 17- (n-pentyl carbonate).

Example 71

a) 1 g of 6α-fluoro-prednisolone 17- (n-pentyl carbonate) in place of methylchloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) React with 1.3 ml of cyclopentylpropionyl chloride in the same manner as in Example 4a) and complete

1) 6α-fluoro-prednisolone 17- (n-pentyl carbonate) -21 (methyl carbonate),

2) 6α-fluoro-prednisolone 17- (n-pentyl carbonate) -21- (ethyl carbonate),

3) 6α-fluoro-prednisolone 17- (n-pentyl carbonate) -21- (n-propyl carbonate),

4) 6α-fluoro-prednisolone 17- (n-pentyl carbonate) -21- (n-butyl carbonate),

5) 6α-fluoro-prednisolone 17- (n-pentyl carbonate) -21- (isopropylcarbonate),

6) 6α-fluoro-prednisolone 17- (n-pentyl carbonate) -21- (isobutyl carbonate),

7) 6α-fluoro-prednisolone 17- (n-pentyl carbonate) -21-acetate,

8) 6α-fluoro-prednisolone 17- (n-pentyl carbonate) -21-propionate,

9) 6α-fluoro-prednisolone 17- (n-pentyl carbonate) -21-butyrate,

10) 6α-fluoro-prednisolone 17- (n-pentyl carbonate) -21-valerate,

11) 6α-fluoro-prednisolone 17- (n-pentyl carbonate) -21-cyclopropanecarboxylate,

12) 6α-fluoro-prednisolone 17- (n-pentyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 6α-fluoro-prednisolone 17- (n-pentyl carbonate) was reacted with methanesulfonyl chloride in the same manner as in Example 2f), and the product was completed and crystallized in ether to give 6α-fluoro-prednisolone 17- (n-pentyl carbonate) -21-methanesulfonate is obtained.

Using the same moles of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride in place of methanesulfonyl chloride, the corresponding 6α-fluoro-prednisolone 17- (n-pentyl carbonate) -21-P-toluene Sulfonate or 6α-fluoro-prednisolone 17- (n-pentyl carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)은 독일연방공화국 특허 제1,668,079호에 제시된 바에 따라 6α-플루오로-프레드니솔론과 테트라-(n-펜틸)오르토 카보네이트로부터 제조한다.c) 6α-fluoro-prednisolone di- (n-pentyl) ortho carbonate (Rf required for the first time in the reaction)

0.6) is prepared from 6α-fluoro-prednisolone and tetra- (n-pentyl) ortho carbonate as set forth in Federal Republic of Germany Patent No. 1,668,079.

0.4)를 얻는다.The first mentioned compound was then hydrolyzed by the method of Example 1c) to give 6α-fluoro-prednisolone 17- (n-pentyl carbonate) (Rf

0.4).

Example 72

a) 1 g of 16α- or β-methyl-prednisolone 17- (n-pentyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1.3 ml of cyclopropane carboxylic acid chloride,

12) React with 1.3 ml of cyclopentyl propionyl chloride in the same manner as in Example 4a) and complete

1) 16α- or β-methyl-prednisolone 17- (n-pentyl carbonate) -21- (methyl carbonate),

2) 16α- or β-methyl-prednisolone 17- (n-pentyl carbonate) -21- (ethyl carbonate),

3) 16α- or β-methyl-prednisolone 17- (n-pentyl carbonate) -21- (n-propyl carbonate),

4) 16α- or β-methyl-prednisolone 17- (n-pentyl carbonate) -21- (n-butyl carbonate),

5) 16α- or β-methyl-prednisolone 17- (n-pentyl carbonate) -21- (isopropyl carbonate),

6) 16α- or β-methyl-prednisolone 17- (n-pentyl carbonate) -21- (isobutyl carbonate),

7) 16α- or β-methyl-prednisolone 17- (n-pentyl carbonate) -21-acetate,

8) 16α- or β-methyl-prednisolone 17- (n-pentyl carbonate) -21-propionate,

9) 16α- or β-methyl-prednisolone 17- (n-pentyl carbonate) -21-butyrate,

10) 16α- or β-methyl-prednisolone 17- (n-pentyl carbonate) -21-valorate,

11) 16α- or β-methyl-prednisolone 17- (n-pentyl carbonate) -21-cyclopropanecarboxylate,

12) 16α- or β-methyl-prednisolone 17- (n-pentyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 16α- or β-methyl-prednisolone 17- (n-pentyl carbonate) is reacted with methanesulfonyl chloride by the method of Example 2f) and the product is completed and crystallized in ether to give 16α- or β-methyl- Prednisolone 17- (n-pentyl carbonate) -21-methanesulfonate is obtained.

Using the same moles of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methanesulfonyl chloride, the corresponding 16α- or β-methyl-prednisolone 17- (n-pentyl carbonate) -21-P- Toluenesulfonate or 16α- or β-methyl-prednisolone 17- (n-pentyl carbonate) -21-P-chloro benzenesulfonate is obtained.

0.6)은 독일연방공화국 특허원 제1,668,079호의 16α-또는 β-메틸-프레드니솔론과 테트라-(n-펜틸)오르토 카보네이트에 의해 만든다.c) 16α- or β-methyl-prednisolone di- (n-pentyl) orthocarbonate (Rf required for the first time in the reaction)

0.6) is made from 16α- or β-methyl-prednisolone and tetra- (n-pentyl) ortho carbonates of Federal Patent Application No. 1,668,079.

0.4)를 얻는다.Next, the first mentioned compound was hydrolyzed in the same manner as in Example 1c) to give 16α- or β-methyl-prednisolone 17- (n-pentyl carbonate) (Rf

0.4).

Example 73

a) 1 g of 6α, 16α- or β-dimethyl-prednisolone 17- (n-pentyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate, and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) Reacting with 1.3 ml of cyclopentylpropionyl chloride in the same manner as in Example 4a) and completing

1) 6α, 16α- or β-dimethyl-prednisolone 17- (n-pentyl carbonate) -21- (methyl carbonate),

2) 6α, 16α- or β-dimethyl-prednisolone 17- (n-pentyl carbonate) -21- (ethyl carbonate),

3) 6α, 16α- or β-dimethyl-prednisolone 17- (n-pentyl carbonate) -21- (n-propyl carbonate),

4) 6α, 16α- or β-dimethyl-prednisolone 17- (n-pentyl carbonate) -21- (n-butyl carbonate),

5) 6α, 16α- or β-dimethyl-prednisolone 17- (n-pentyl carbonate) -21- (isopropylcarbonate),

6) 6α, 16α- or β-dimethyl-prednisolone 17- (n-pentyl carbonate) -21- (isobutyl carbonate),

7) 6α, 16α- or β-dimethyl-prednisolone 17- (n-pentyl carbonate) -21-acetate,

8) 6α, 16α- or β-dimethyl-prednisolone 17- (n-pentyl carbonate) -21-propionate,

9) 6α, 16α- or β-dimethyl-prednisolone 17- (n-pentyl carbonate) -21-butyrate,

10) 6α, 16α- or β-dimethyl-prednisolone 17- (n-pentyl carbonate) -21-valorate,

11) 6α, 16α- or β-dimethyl-prednisolone 17- (n-pentyl carbonate) -21-cyclopropyl carboxylate,

12) 6α, 16α- or β-dimethyl-prednisolone 17- (n-pentyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 6α, 16α- or β-dimethyl-prednisolone 17- (n-pentyl carbonate) is reacted with methanesulfonyl chloride in the same manner as in Example 2f) and the product is completed and crystallized in ether to give 6α, 16α or β-dimethyl-prednisolone 17- (n-pentyl carbonate) -21-methanesulfonate is obtained.

Using the same moles of P-toluene sulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methanesulfonyl chloride, the corresponding 6α, 16α- or β-dimethyl-prednisolone 17- (n-pentyl carbonate) -21-P Toluenesulfonate and 6α, 16α- or β-dimethyl-prednisolone 17- (n-pentyl carbonate) -21-P-chloro benzenesulfonate are obtained.

0.6)은 독일연방공화국 특허원 제1,668,079호에 제시된 바에 따라 6α, 16α-또는 β-디메틸-프레드니솔론과 테트라-(n-펜틸)오르토 카보네이트로부터 제조한다.c) 6α, 16α- or β-dimethyl-prednisolone di- (n-pentyl) orthocarbonate (Rf required for the first time in the reaction)

0.6) are prepared from 6α, 16α- or β-dimethyl-prednisolone and tetra- (n-pentyl) ortho carbonates as set forth in Federal Patent Application No. 1,668,079.

0.4)를 얻는다.The first mentioned compound was then hydrolyzed by the method of Example 1c) to give 6α, 16α- or β-dimethyl-prednisolone 17- (n-pentyl carbonate) (Rf

0.4).

Example 74

a) 1 g of 9α-chloro-16α-methyl-prednisolone 17- (n-pentyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) React with 1.3 ml of cyclopentylpropionyl chloride in the same manner as in Example 4a) and complete the corresponding

1) 9α-chloro-16α-methyl-prednisolone 17- (n-pentyl carbonate) -21- (methyl carbonate),

2) 9α-chloro-16α-methyl-prednisolone 17- (n-pentyl carbonate) -21- (ethyl carbonate),

3) 9α-chloro-16α-methyl-prednisolone 17- (n-pentyl carbonate) -21- (n-propyl carbonate),

4) 9α-chloro-16α-methyl-prednisolone 17- (n-pentyl carbonate) -21- (n-butyl carbonate),

5) 9α-chloro-16α-methyl-prednisolone 17- (n-pentyl carbonate) -21- (isopropyl carbonate),

6) 9α-chloro-16α-methyl-prednisolone 17- (n-pentyl carbonate) -21- (isobutyl carbonate),

7) 9α-chloro-16α-methyl-prednisolone 17- (n-pentyl carbonate) -21-acetate,

8) 9α-chloro-16α-methyl-prednisolone 17- (n-pentyl carbonate) -21-propionate,

9) 9α-chloro-16α-methyl-prednisolone 17- (n-pentyl carbonate) -21-butyrate,

10) 9α-chloro-16α-methyl-prednisolone 17- (n-pentyl carbonate) -21-valorate,

11) 9α-chloro-16α-methyl-prednisolone 17- (n-pentyl carbonate) -21-cyclopropane carboxylate,

12) 9α-chloro-16α-methyl-prednisolone 17- (n-pentyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 9α-chloro-16α-methyl-prednisolone 17- (n-pentyl carbonate) was reacted with methanesulfonyl chloride in the same manner as in Example 2f) and the product was completed and crystallized in ether to give 9α-chloro-16α -Methyl-prednisolone 17- (n-pentyl carbonate) -21-methanesulfonate is obtained.

If the same moles of P-toluenesulfonyl chloride or P-chlorobenzene sulfonyl chloride were used instead of methanesulfonyl chloride, the corresponding 9α-chloro-16α-methyl-prednisolone 17- (n-pentyl carbonate) -21-P -Chloro benzenesulfonate is obtained.

0.6)은 독일연방공화국 특허 제1,668,079호에 제시된 바에 따라 9α-클로로-16α-메틸-프레드니솔론과 테트라-(n-펜틸)오르토 카보네이트로 부터 제조한다.c) 9α-chloro-16α-methyl-prednisolone di- (n-pentyl) orthocarbonate (Rf first required for the reaction)

0.6) is prepared from 9α-chloro-16α-methyl-prednisolone and tetra- (n-pentyl) ortho carbonate as set forth in German Patent No. 1,668,079.

0.4)를 얻는다.Next, the first mentioned compound was hydrolyzed in the same manner as in Example 1c) to give 9α-chloro-16α-methyl-prednisolone 17- (n-pentyl carbonate) (Rf

0.4).

Example 75

a) 1 g of 9α-chloro-prednisolone 17- (n-pentyl carbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate,

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml propionyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) React with 1.3 ml of cyclopentylpropionyl chloride in the same manner as in Example 4a) and complete the corresponding

1) 9α-chloro-prednisolone 17- (n-pentyl carbonate) -21- (methyl carbonate),

2) 9α-chloro-prednisolone 17- (n-pentyl carbonate) -21- (ethyl carbonate),

3) 9α-chloro-prednisolone 17- (n-pentyl carbonate) -21- (n-propyl carbonate),

4) 9α-chloro-prednisolone 17- (n-pentyl carbonate) -21- (n-butyl carbonate),

5) 9α-chloro-prednisolone 17- (n-pentyl carbonate) -21- (isopropylcarbonate),

6) 9α-chloro-prednisolone 17- (n-pentyl carbonate) -21- (isobutyl carbonate),

7) 9α-chloro-prednisolone 17- (n-pentyl carbonate) -21-acetate,

8) 9α-chloro-prednisolone 17- (n-pentyl carbonate) -21-propionate,

9) 9α-chloro-prednisolone 17- (n-pentyl carbonate) -21-butyrate,

10) 9α-chloro-prednisolone 17- (n-pentyl carbonate) -21-valerate,

11) 9α-chloro-prednisolone 17- (n-pentyl carbonate) -21-cyclopropane carboxylate,

12) 9α-chloro-prednisolone 17- (n-pentyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of 9α-chloro-prednisolone 17- (n-pentyl carbonate) was reacted with methanesulfonyl chloride by the method of Example 2f) and the product was completed and crystallized in ether to give 9α-chloro-prednisolone 17- (n- Pentyl carbonate) -21-methanesulfonate is obtained.

If the same moles of P-toluenesulfonyl chloride or P-chlorobenzenesulfonyl chloride are used instead of methanesulfonate, the corresponding 9α-chloro-prednisolone 17- (n-pentyl carbonate) -21-P-toluenesulfonate or 9α Chloro-prednisolone 17- (n-pentyl carbonate) -21-P-chlorobenzene sulfonate is obtained.

0.6)은 독일연방공화국 특허 제1,668,079호에 제시된 바에 따라 9α-클로로-프레드니솔론과 테트라-(발레릴)오르토 카보네이트로 부터 제조한다.c) 9α-chloro-prednisolone di- (n-pentyl) ortho carbonate (Rf required for the first time in the reaction)

0.6) is prepared from 9α-chloro-prednisolone and tetra- (valeryl) ortho carbonate, as set forth in Federal Republic of Germany Patent No. 1,668,079.

0.4)를 제조한다.Next, the first mentioned compound was hydrolyzed in the same manner as in Example 1c) to give 9α-chloro-prednisolone 17- (n-pentyl carbonate) (Rf

0.4) is prepared.

Example 76

6 g of 6, 16α-dimethyl-4,6-prenadiene-11β, 17α-21-triol-3, 2-c-2-phenylpyrazole (bimedrazole) are dissolved in 125 g of pure dioxane and then 500 mg of P-toluenesulfonic acid and 16.5 ml of tetraethyl ortho carbonate are added.

After stirring at 20 ° C. for 6 hours, several drops of pyridine are dropped to neutralize acidity. The reaction mixture is added to water to produce an oil phase precipitate. This is filtered through a fluid filter. The oil is absorbed in methylene chloride and the extract is washed with water and distilled off in vacuo. 7.9 g of bimedrazole 17, 21- (diethyl carbonate) are obtained in the form of a foam.

IR (KBr): 3,560, 3,460, 2,980, 2,880, 1,720, 1,595, 1,500, 1,200, 1,130, 1,035, 755cm ^-1

UV (CH ₃ OH): λmax = 312μ (ε = 20,600)

λmax = 280μ (ε = 17,100)

TLC (solvent: methylene chloride / methanol = 19: 1, feed 1)

Rf = 0.45 (reaction product) and Rf = 0.10 (starting material, bimedrazole).

Example 77

a) 120 ml of glycial acetic acid and 0.6 ml of water mixed solution containing 3 g of bimedrazole 17,21- (diethyl) ortho carbonate are left at 22 ° C. for 5 hours.

TLC showed that after this time there was an optimal amount of bimerazole 17- (ethyl carbonate) desired. The reaction mixture is added to 1.5 L of water and the pH adjusted to 5 with ammonia solution to separate the amorphous precipitate. After filtration, washing with water and drying gave 2.8 g of amorphous bimedrazole 17- (ethyl carbonate).

IR: 3,420 to 3,500 (wide), 2,940, 2,880, 1,735, 1,715, 1,595, 1,500, 1,265, 760 cm ^-1

TLC: Rf = 0.25

UV: λmax ₁ = 312μ (ε = 20,600)

λmax ₂ = 280 μ (ε = 17,100)

Example 78

a) 1 g of bimedrazole 17- (ethylcarbonate) in place of methyl chloroformate

1) 0.8 ml methyl chloroformate and

2) 0.8 ml of ethyl chloroformate,

3) 0.9 ml of n-propyl chloroformate,

4) 0.9 ml of n-butyl chloroformate,

5) 1.0 ml of isopropyl chloroformate,

6) 1.0 ml of isobutyl chloroformate,

7) 0.8 ml of acetyl chloride,

8) 0.8 ml of propyl chloride,

9) 0.9 ml of butyryl chloride,

10) 1 ml of valeryl chloride,

11) 1 ml of cyclopropane carboxylic acid chloride,

12) React with 1.3 ml of cyclopentylpropionyl chloride in the same manner as in Example 4a) and complete the corresponding

1) bimedrazole 17- (ethyl carbonate) -21- (methyl carbonate),

2) bimedrazole 17- (ethyl carbonate) -21- (ethyl carbonate),

3) bimedrazole 17- (ethyl carbonate) -21- (n-propyl carbonate),

4) bimedrazole 17- (ethyl carbonate) -21- (n-butyl carbonate),

5) bimedrazole 17- (ethyl carbonate) -21- (isopropyl carbonate),

6) bimedrazole 17- (ethyl carbonate) -21- (isobutyl carbonate),

7) bimedrazole 17- (ethyl carbonate) -21- (acetate),

8) bimedrazole 17- (ethyl carbonate) -21-propionate,

9) bimedrazole 17- (ethyl carbonate) -21-butyrate,

10) bimedrazole 17- (ethyl carbonate) -21-valerate,

11) bimedrazole 17- (ethyl carbonate) -21-cyclopropane carboxylate,

12) Bimedrazole 17- (ethyl carbonate) -21-cyclopentyl propionate is obtained.

b) 3 g of bimedrazole 17- (ethyl carbonate) was reacted with methanesulfonyl chloride in the same manner as in Example 2f), and the product was completed and crystallized in ether to give bimedrazole 17- (ethyl carbonate) -21-methane Sulfonate is obtained.

Equivalent molar amounts of P-toluenesulfonyl chloride or P-chlorobenzenesulfonyl chloride instead of methane chloride can be used to produce the corresponding bimerazole 17- (ethyl carbonate) -21-P-toluenesulfonate and bimethazole 17- ( Ethyl carbonate) -21-P-chloro benzenesulfonate is obtained.

Example 79

Suitable bimerazole 17- (n-propyl carbonate) -21-carboxylate, bimedrazole 17- (n-propyl carbonate) -21-carbonate and bimedrazole 17- (n-propyl carbonate) -21-sulfonate The bimerazole 17- (n-propyl carbonate) (method: bimethazole + tetra- (n-propyl) orthocarbonate is used in place of tetraethylortho carbonate in the above-described manner. Di- (n-propyl orthocarbonate) is produced, which is optionally soluble in acetic acid / water).

Example 80

1 ml of anhydrous chloroacetate is added to 30 ml of pure tetrahydrofuran and 8 ml of pure pyridine solution containing 1 g of dexamethasone 17- (ethyl carbonate) at 20 ° C. The stirred reaction mixture is poured into water containing sodium chloride for about 3 days at room temperature.

The mixture is extracted with methylene chloride, the extract is washed with water, dried in vacuo and concentrated.

Recrystallization from acetone / ether gives dexamethasone 17- (ethyl carbonate) -21-chloroacetate (melting point 209 ° C.) in the form of a foam.

IR: 3460, 1730, 1660, 1615, 1600, 1260, cm ^-1

MS: M = 540

Cortisol 17- (ethyl carbonate), Cortisone 17- (ethyl carbonate) prednisolone 17- (ethyl carbonate) prednisolone 17- (ethyl carbonate), 6α-methylprednisolone 17- (ethyl carbonate), 6α-fluoro-prednisolone 17- ( Ethyl carbonate), betamethasone 17- (ethyl carbonate), beclomethasone 17- (ethyl carbonate), 9α-chloro-16α-methyl-prednisolone 17- (ethyl carbonate) and 9α-fluoro-dexamethasone 17- (ethyl carbonate ) Is used in place of dexamethasone 17- (ethyl carbonate) to obtain 21-chloro acetate of the corresponding listed corticoid 17- (ethyl carbonate) in a similar manner.

Instead of dexamethasone 17- (ethyl carbonate) and another corticoid 17- (ethyl carbonate) of one of the listed ones, using the corresponding corticoid 17- (n-propyl carbonate) would result in the corresponding corticoid 17- (n-propyl carbonate) ) -21-chloroacetate is obtained in a similar manner.

Example 81

2 ml of CrO ₃ oxidant solution (preparation: 13.36 g of CrO ₃ is dissolved in 30 ml of water. 11.5 ml of concentrated sulfuric acid is cooled with ice and added dropwise to make 50 ml of the mixture). 2.5 g of dexamethasone 17, 21- To 75 ml of an acetone solution for analysis containing bis- [ethyl carbonate] (prepared by Example 2) was added dropwise while stirring at 0 ° C. After stirring for 1 hour at 0 ° C. for 1.5 hours at 20 ° C., the reaction mixture is poured into water containing the amount of pyridine or alkali metal bicarbonate necessary for neutralization. The mixture is extracted repeatedly with methylene chloride and the extract is washed with water, dried in vacuo and concentrated. The resulting foam was recrystallized from acetone / diisopropyl ether to give 2.1 g of 11-dihydro-dexamethasone 17,21-bis [ethyl carbonate] (melting point: 212 ° C.).

The band no longer appears in the region of IR: 1,720 to 1735, 1660, 1625, 1280, 1260 cm ⁻¹ 3420 cm ⁻¹ (OH).

MS: M ⁺ = 533.5

Instead of dexamethasone 17,21-bis- [ethyl carbonate] in the above-described oxidation reaction, a hydroxy group at the 11-position and a (alkyl carbonate) group at the 21-position, an alkyl carboxylate group or Corticoid 17-alkyl carbonates containing alkyl- or aryl-sulfonate groups) can be used for the corresponding 11-dehydro-corticoid 17-alkyl carbonates) -21- (alkyl carbonates), 11-dehydro-corptico Id 17- (alkyl carbonate) -21-alkyl carboxylate, 11-dihydro-corticoid 17- (alkyl carbonate) -21-alkyl sulfonate and 11-dehydro-corticoid 17- (alkylcarbonate) -21-aryl sulfo Nates are obtained in a similar way.

Example 82

1.71 g propionate chloride is added dropwise with stirring at 0 ° C. to 68 ml pyridine solution containing 6.85 g prednisolone 17-ethyl carbonate. After stirring at 0 ° C. for 0.5 hours at 22 ° C. for 2 hours, the solution is poured into 2 liters of water containing 100 g of sodium chloride. The precipitate is filtered off, washed with water and dried in P ₂ O ₅ overhead air. The obtained 6.3 g of prednisolone 17-ethyl carbonate-21-propionate can be seen that a small amount of impurities still exist by TLC. Chromatography with toluene / ethyl acetate 8: 2 on 300 g of silica gel (column diameter: 3 cm) to make the product very pure. TLC is performed to combine the fractions showing a single spot at Rf = 0.27 (toluene / ethyl acetate 6:35), the eluent is distilled off and the product is crystallized in diisopropyl ether. 4.9 g of prednisolone 17- (ethyl carbonate-21-propionate) (melting point: 112 ° C.) are obtained.

UV: λmax = 241 nm, ε = 15800

IR: 3430, 1730, 1650, 1610, 1270, 1235cm ^-1

Example 83

The reaction product is obtained by reacting 68 ml of pyridine solution containing 6.85 g of prednisolone 17-ethyl carbonate with 1.7 g of acetic anhydride by the method described in Example 83, which is purified by chromatography. Prednisolone 17-ethyl carbonate-21-acetate having a melting point of 102 DEG C of 4.8 g is obtained.

UV: λmax = 240nm, ε = 15400

IR: 3440, 1725, 1655, 1620, 1270, 1230cm ^-1

Example 84

By the method in Example 83, 68 ml of a pyridine solution containing 6.85 g of prednisolone 17-n-propyl carbonate was reacted with 2 g of propionic acid chloride to give the product which was purified by chromatography. 5.2 g of Predsolone 17-n-propyl carbonate-21-propionate (melting point: 108 ° C.) is obtained.

UV: λmax = 241 nm, ε = 15500

IR: 3450, 1730, 1650, 1610, 1270, 1230cm ^-1

Example 85

By the method in Example 83, 68 ml of a pyridine solution containing 6.85 g of prednisolone 17-n-propyl carbonate was reacted with 1.7 g of acetic anhydride to produce a reaction product which was purified by chromatography. Prednisolone 17-n-propyl carbonate-21-acetate having a melting point of 98 ° C. of 5.0 g is obtained.

UV: lambda max = 242nm, ε = 15300

IR: 3440, 1730, 1660, 1620, 1270, 1230cm ^-1

Example 86

The method in Example 83 reacted 68 ml of pyridine solution containing 6.85 g of Cortisol 17-ethyl carbonate with 1.7 g of propionic acid chloroide to produce a reaction product which was purified by chromatography. Cortisol 17-ethyl carbonate-21-propionate having a melting point of 104 ° C. of 4.9 g is obtained.

UV: λmax = 242 nm, ε = 15600

IR: 3440, 1730, 1655, 1610, 1270, 1230cm ^-1

Example 87

The method in Example 83 reacts 68 ml of pyridine solution containing 6.85 g of Cortisol 17-n-propyl carbonate with 1.8 g of propionic acid chloride to produce a reaction product which is purified by chromatography. Cortisol 17-n-propylcarbonate-21-propionate with a melting point of 110 ° C. of 5.1 g is obtained.

UV: lambda max = 242nm, ε = 15400

IR: 3440, 1730, 1660, 1615, 1270, 1230cm ^-1

Example 88

150 ml of glacial acetic acid solution containing 1 ml of water containing 12.5 g of prednisolone 17,21-diethyl-orthocarbonate (prednisolone and teraethyl-orthocarbonate (produced by Federal Republic of Germany Patent No. 1,668,079)) at 20 ° C The mixture is left for 2 hours and then poured into 2 liters of water containing 100 g of sodium chloride The precipitate is filtered, washed with water and dried under high vacuum on P ₂ O ₅ , which can be used to further advance the reaction without post-treatment. 7.2 g of prednisolone 17-ethyl carbonate are obtained.

Extraction with methyl chloride, washing with water, distillation, crystallization with diisopropyl ether yields 3.6 g of another prednisolone 17-ethyl carbonate.

UV: λmax = 241 nm, ε = 15300

IR: 3450, 1730, 1650, 1265cm ^-1

Example 89

12.5 g of prednisolone 17,21-di-n-propyl-orthocarbonate) prepared in accordance with Example 89 according to Federal Republic of Germany Patent No. 1,668,079 from rednisolone and tetra-n-propyl-orthocarbonate) By reaction to completely separate the reaction product. A total amount of 10.7 g of prednisolone 17-n-propyl carbonate is obtained.

UV: λmax = 241 nm, ε = 15400

IR: 3440, 1730, 1650, 1610, 1270cm ^-1

Example 90

The method of Example 89 was reacted with 12.5 g of Cortisol 17,21-diethyl-orthocarbonate (prepared from Cortisol and tetraethyl-ortho carbonate according to Federal Patent No. 1,668,079) and the reaction product was completely separated. . 10.2 g of Cortisol 17-ethyl carbonate are obtained.

UV: λmax = 242 nm, ε = 15600

IR: 3450, 1730, 1655, 1615, 1270cm ^-1

Example 91

Reaction was carried out by reacting 12.5 g of Cortisol 17,21-di-n-propyl-orthocarbonate (produced by Federal Republic of Germany Patent No. 1,668,079 from cortisol and tetra-n-propyl-orthocarbonate) by the method of Example 89. Completely separate the product.

10 g of cortisol 17-n-propyl carbonate are obtained.

UV: lambda max = 242nm, ε = 15400

IR: 3450, 1730, 1655, 1615, 1270cm ^-1

Claims (1)

The corticosteroid 17,21- (dialkylorthocarbonates) of the following general formula (II) was hydrolyzed to obtain the steroid 17- (monoalkyl carbonates) of the following general formula (III).

With carboxylic acid halides or carboxylic anhydrides containing groups or

With halogeno formate containing groups or

A method for preparing a steroid 17- (alkyl carbonate) of the general formula (I) by reacting an aliphatic or aromatic sulfonic acid halide containing a group at the 21-position (when R ₁ ? H, the OH group at the 11 position Oxidize).

Where A is

Or C = 0 group or if a 9,11-position double bond is present, CH group, Y represents hydrogen, fluorine or chlorine, Z represents hydrogen, chlorine, fluorine or methyl group and R ₁ is hydrogen , Acyl group of the following general formula (a)

Wherein R ₄ is hydrogen or a straight or branched aliphatic hydrocarbon group of 1 to 10 carbon atoms, or an alicyclic hydrocarbon group of 3 to 8 carbon atoms and n- is an integer of 0 to 4 or if n ≠ 0, then R ₄ is halogen or

Wherein R 'and R' are the same or different and are hydrogen or an alkyl group having 1 to 4 carbon atoms or R 'and R' together with nitrogen represent a saturated heterocyclic structure of 5 to 7 elements.) Or a carbonyloxyalkyl group of the following general formula (b)

Wherein n and R ₄ are as defined above and R ≠ H when n is 0 and R ₄ represents only halogen when n is 2 to 4 or an aliphatic or aromatic sulfonic acid ester of formula (c)

(Wherein R ₅ is alkyl having 1 to 4 carbon atoms, phenyl, methylphenyl, ethylphenyl, fluorophenyl, bromophenyl or chlorophenyl) and R ₂ is a straight or branched alkyl group having 1 to 8 carbon atoms, R ₃ represents hydrogen, methyl in the α or β-position, fluorine, or a methyl group optionally substituted with one or two fluorine atoms, and 1,2- and / or 2,3- and / or 6,7-and ( Or) an additional double bond may be present at the 9,11-position

Denotes a pyrazole ring which is fused at positions 2 and 3 of the 3-deoxo-steroid backbone and may have an alkyl group having 1 to 4 carbon atoms or an optionally halogen substituted phenyl group at one atom of the two nitrogen atoms.