CN104447930A - Preparation method of 16a,17a-dyhydroxyl-21-acetoxyl-1,4-pregnene diene-3,11,20-triketone - Google Patents
Preparation method of 16a,17a-dyhydroxyl-21-acetoxyl-1,4-pregnene diene-3,11,20-triketone Download PDFInfo
- Publication number
- CN104447930A CN104447930A CN201410480127.8A CN201410480127A CN104447930A CN 104447930 A CN104447930 A CN 104447930A CN 201410480127 A CN201410480127 A CN 201410480127A CN 104447930 A CN104447930 A CN 104447930A
- Authority
- CN
- China
- Prior art keywords
- triketone
- nitrae
- isosorbide
- reaction
- acetoxyl group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 0 C[C@@]1(CC2O)[C@@](*)(C*)CCC1C(CC1)C2[C@@](C)(C=C2)C1=CC2=O Chemical compound C[C@@]1(CC2O)[C@@](*)(C*)CCC1C(CC1)C2[C@@](C)(C=C2)C1=CC2=O 0.000 description 2
- NHVKTAGIUONXJA-AGSCGBNJSA-N C[C@](CC1O)(C(CC2)C(CCC3C4)C1[C@@]3(C)C=CC4=O)[C@]2(C(CO)=O)O Chemical compound C[C@](CC1O)(C(CC2)C(CCC3C4)C1[C@@]3(C)C=CC4=O)[C@]2(C(CO)=O)O NHVKTAGIUONXJA-AGSCGBNJSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0046—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa
- C07J5/0061—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention provides a preparation method of 16a,17a-dyhydroxyl-21-acetoxyl-1,4-pregnene diene-3,11,20-triketone. The preparation method comprises the following steps: step 1, by taking prednisone as a raw material, allowing the prednisone to have an esterification reaction with acetic oxide; step 2, performing a degreasing reaction by use of alkali; and step 3, oxidizing by use of potassium permanganate under an acidic condition. The method has the advantages of adopting raw materials which are low in cost and easy to obtain, simplifying the production process route and being simple to operate and suitable for large-scale industrial production.
Description
Technical field
The present invention relates to 16a, the preparation method of 17a-dihydroxyl-21-acetoxyl group-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone.
Background technology
16a, 17a-dihydroxyl-21-acetoxyl group-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone is the intermediate of synthesis anti-inflammatory drug budesonide.
United States Patent (USP) 4695625 to disclose with 16a-hydroxy prednisonlone as raw material through single step reaction to prepare the chemical synthesis process of budesonide, but this method cost of material is high, does not have to announce how to control reaction conditions and make product meet the requirement of European Pharmacopoeia; It is the synthesis route that starting raw material prepares budesonide that Chinese patent 101279997 B discloses with prednisolone acetate, although reactions steps is short, but because of the reason that selection and the reaction conditions of raw material are arranged, exist and to eliminate and oxidation time is grown and the shortcoming such as yield is low, industrialization cost is too high; It is the operational path of starting raw material that Chinese patent 101863952B discloses with prednisolone; although raw material is easy to get; price is low; but because 11 exist hydroxyl, be not easy to make three hydroxyl all acetylizes in acetic anhydride protection hydroxyl, and when being hydrolyzed, be not easy the acetoxyl group taking off 11 below; when potassium permanganate oxidation; side reaction is many, and product is very complicated, and yield is low.16a, 17a-dihydroxyl-21-acetoxyl group-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone is the key intermediate of synthesis budesonide, and the synthesis technique therefore studying it has very large value.
Summary of the invention
In order to overcome the problems referred to above, the object of the present invention is to provide a kind of preparation method of 16a, 17a-dihydroxyl-21-acetoxyl group-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone, often walk reaction yield in the method all high, side reaction is few.
The present inventor is found by test of many times, adopts prednisone as starting raw material, comprises the following steps:
(1) prednisone and acetic anhydride are carried out esterification, obtain intermediate 17a, 21-diacetoxy-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone.
(2) above-mentioned intermediate 17a, 21-diacetoxy-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-diketone alkali or basic metal are carried out degreasing reaction, obtain intermediate 21-acetoxyl group-Isosorbide-5-Nitrae, 16-pregnen diethylene-3,11,20-triketone.
(3) by above-mentioned intermediate 21-acetoxyl group-Isosorbide-5-Nitrae, 16-pregnen diethylene-3,11,20-diketone with potassium permanganate oxidation, obtains target product 16a, 17a-dihydroxyl-21-acetoxyl group-1 under acidic solution does catalysts conditions, 4-pregnen diethylene-3,11,20-triketone.
Synthetic route is as follows:
Concrete technical scheme of the present invention is as follows:
Step (1): the liquor ratio of prednisone, ethyl acetate and acetic anhydride is 1: 2: 2, and tosic acid makees catalyzer, 70 DEG C of reaction 2h; Step (2): make solvent with DMF, Potassium ethanoate and raw materials quality are than 1: 1, and 105 DEG C are reacted 5h; Step (3): make solvent with acetone, potassium permanganate makees oxygenant, and acetic acid makees catalyzer ,-5 DEG C-0 DEG C reaction 30min;
Do raw material with prednisone herein, in the synthesis of intermediate 17a, 21-diacetoxy-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone, make catalyzer with tosic acid, ethyl acetate makees solvent, and backflow, with acetic anhydride double esterification reaction; Intermediate 21-acetoxyl group-1,4, the pregnant steroid triolefin-3 of 16-, 11, the synthesis of 20-triketone: be first dissolved in DMF by Potassium ethanoate and distill, except anhydrating and a small amount of lower-boiling impurity, after the DMF steamed reaches constant boiling point, add previous step reaction product again after mixed solution being cooled to 100 DEG C, avoid the side reaction that the factors such as water cause; 16a, 17a-dihydroxyl-21-acetoxyl group-Isosorbide-5-Nitrae-pregnen diethylene-3, the synthesis of 11,20-triketone: previous step product is dissolved in acetone and is placed in cold well, the acetone of potassium permanganate and the mixing solutions of water slowly drip in reaction solution, vigorous stirring, oxidization-hydrogenation ratio brings up to 80%.
Accompanying drawing explanation
Fig. 1 is synthesis route figure of the present invention.
Embodiment
Below in conjunction with embodiment, the present invention is described in further detail.
Embodiment 1
1) in the reaction flask of a 500ml drying; add 35.8g raw material prednisone (0.1mol), 70ml ethyl acetate, 71.6ml acetic anhydride, 0.35g tosic acid, load onto reflux condensing tube, stir under nitrogen protection and heat up and temperature control 70 DEG C reaction 2h.TLC detection reaction terminates rear cool to room temperature, boil off ethyl acetate, then add 100ml water washing, filter, crude product is obtained after filter cake cryodrying, product obtains white solid powder A (17a, 21-diacetoxy-Isosorbide-5-Nitrae-pregnen diethylene-3 through separating-purifying, 11,20-triketone) 42g, yield 95%, mp:225-226 DEG C.
2) first 42g Potassium ethanoate is dissolved in 220ml DMF and distills, except anhydrating and a small amount of lower-boiling impurity, after the DMF steamed reaches constant boiling point, previous step reaction product A42g (0.095mol) and 200ml DMF solution is added again, 105 DEG C of reaction 5h after mixed solution being cooled to 100 DEG C.TLC tracing detection is reacted to completely.Be down to room temperature, reaction solution slowly poured in 200ml frozen water under stirring, separate out off-white powder.Filter, filter cake 100ml × 2 water washings, obtain crude product after drying, product obtains off-white powder B (21-acetoxyl group-Isosorbide-5-Nitrae, 16-pregnen diethylene-3,11,20-triketone) 35.5g through separating-purifying, yield 93%, mp:207-209 DEG C.
3) 35.5g intermediate B (0.09mol) added in there-necked flask, add 200ml acetone, 5.4g acetic acid, be placed in cold well and be cooled to-5 DEG C.The acetone of 15.8g (0.1mol) potassium permanganate and the mixing solutions 300ml of water is slowly dripped in reaction solution, vigorous stirring, after HPLC detection 30min has reacted, 12.6g sodium bisulfite (0.1mol) is added in reaction solution, stir, filter, filter cake 3 × 50ml washing with acetone, merging filtrate.After filtrate concentrates out acetone, add 200ml elutriation brilliant, leave standstill, suction filtration, dry light yellow solid C (16a, 17a-dihydroxyl-21-acetoxyl group-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone), product obtains white solid powder 30g through acetone recrystallization, yield 80%, mp:222-224 DEG C.
The present embodiment selects 35.8g (0.1mol) prednisone to be that raw material prepares 16a, and 17a-dihydroxyl-21-acetoxyl group-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone fine work 30g (0.072mol), total molar yield is 70.6%.
Embodiment 2
1) in the reaction flask of a 500ml drying; add 50g raw material prednisone (0.14mol), 100ml ethyl acetate, 100ml acetic anhydride, 0.48g tosic acid, load onto reflux condensing tube, stir under nitrogen protection and heat up and temperature control 60 DEG C reaction 4h.TLC detection reaction terminates rear cool to room temperature, boil off ethyl acetate, then add 150ml water washing, filter, after filter cake cryodrying, obtain crude product, product obtains white solid powder A (17a through separating-purifying, 21-diacetoxy-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone) 53.8g, yield 87%.
2) by 53.8 intermediate A (0.12mol), 250mlDMF, 27g Potassium ethanoate, add in there-necked flask, be heated with stirring to 90 DEG C of reaction 7h, TLC tracing detection and be reacted to completely.Be down to room temperature, reaction solution slowly poured in 300ml frozen water under stirring, separate out off-white powder.Filter, filter cake 150ml × 2 water washings, obtain crude product after drying, product obtains off-white powder B (21-acetoxyl group-Isosorbide-5-Nitrae, 16-pregnen diethylene-3,11,20-triketone) 42g through separating-purifying, yield 91.5%.
3) 42g intermediate B (0.11mol) added in there-necked flask, add 200ml DMF, 5g formic acid (0.11mol), be placed in cold well and be cooled to 0 DEG C-5 DEG C.Add the acetone soln 300ml of 17.4g potassium permanganate, after HPLC detection 30min has reacted, 12.6g sodium bisulfite (0.1mol) added in reaction solution, stirs, filter, filter cake 3 × 50ml washing with acetone, merging filtrate.After filtrate concentrates out acetone, add 200ml elutriation brilliant, leave standstill, suction filtration, dry light yellow solid C (16a, 17a-dihydroxyl-21-acetoxyl group-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone) product obtains white solid powder 29.7g through acetone recrystallization, yield 65%.
The present embodiment selects 50g (0.14mol) prednisone to be that raw material prepares 16a, and 17a-dihydroxyl-21-acetoxyl group-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone fine work 29.7g (0.071mol), total molar yield is 51.7%.
Embodiment 3
1) in the reaction flask of a 500ml drying; add 60g raw material prednisone (0.17mol), 120ml ethyl acetate, 120ml acetic anhydride, 0.48g tosic acid, load onto reflux condensing tube, stir under nitrogen protection and heat up and temperature control 80 DEG C reaction 2h.TLC detection reaction terminates rear cool to room temperature, boil off ethyl acetate, then add 150ml water washing, filter, after filter cake cryodrying, obtain crude product, product obtains white solid powder A (17a through separating-purifying, 21-diacetoxy-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone) 67.8g, yield 90.3%.
2) by 67.8g intermediate A (0.154mol), 300ml DMF, 67.8g sodium-acetate, add in there-necked flask, be heated with stirring to 90 DEG C of reaction 7h, TLC tracing detection and be reacted to completely.Be down to room temperature, reaction solution slowly poured in 300ml frozen water under stirring, separate out off-white powder.Filter, filter cake 150ml × 2 water washings, obtain crude product after drying, product obtains off-white powder B (21-acetoxyl group-Isosorbide-5-Nitrae, 16-pregnen diethylene-3,11,20-triketone) 53.6g through separating-purifying, yield 91.2%.
3) 53.6g intermediate B (0.14mol) added in there-necked flask, add 200ml DMF, 100ml acetone, 6.4g formic acid, stir, be cooled to 10 DEG C.Add 22.1g potassium permanganate (0.14mol) powder in batches, after HPLC detection 30min has reacted, 17.6g sodium bisulfite (0.14mol) added in reaction solution, has stirred, filtered, filter cake 3 × 100ml washing with acetone, merging filtrate.After filtrate concentrates out acetone, add 200ml elutriation brilliant, leave standstill, suction filtration, dry light yellow solid C (16a, 17a-dihydroxyl-21-acetoxyl group-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone) product obtains white solid powder 37.8g through acetone recrystallization, yield 65%.
The present embodiment selects 60g (0.17mol) prednisone to be that raw material prepares 16a, and 17a-dihydroxyl-21-acetoxyl group-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone fine work 37.8g (0.09mol), total molar yield is 53.5%.
Embodiment 4
1) in the reaction flask of a 500ml drying; add 40g raw material prednisone (0.11mol), 80ml ethyl acetate, 60ml acetic anhydride, 0.35g tosic acid, load onto reflux condensing tube, stir under nitrogen protection and heat up and temperature control 70 DEG C reaction 4.5h.TLC detection reaction terminates rear cool to room temperature, boil off ethyl acetate, then add 100ml water washing, filter, after filter cake cryodrying, obtain crude product, product obtains white solid powder A (17a through separating-purifying, 21-diacetoxy-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone) 39.2g, yield 80.6%.
2) by 39.2g intermediate A (0.089mol), 100ml DMF, 100g Potassium ethanoate, add in there-necked flask, be heated with stirring to 90 DEG C of reaction 5h, TLC tracing detection and be reacted to completely.Be down to room temperature, reaction solution slowly poured in 100ml frozen water under stirring, separate out off-white powder.Filter, filter cake 100ml × 2 water washings, obtain crude product after drying, product obtains off-white powder B (21-acetoxyl group-Isosorbide-5-Nitrae, 16-pregnen diethylene-3,11,20-triketone) 31.5g through separating-purifying, yield 92.7%.
3) 31.5g intermediate B (0.08mol) added in there-necked flask, add 200ml DMF, 4.6g formic acid (0.1mol), stir, be cooled to 0 DEG C-5 DEG C.Add the acetone soln 300ml of 25.3g potassium permanganate (0.16mol), after HPLC detection 30mi n has reacted, 10.8g sodium bisulfite (0.08mol) added in reaction solution, has stirred, filtered, filter cake 3 × 50ml washing with acetone, merging filtrate.After filtrate concentrates out acetone, add 200ml elutriation brilliant, leave standstill, suction filtration, dry light yellow solid C (16a, 17a-dihydroxyl-21-acetoxyl group-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone) product obtains white solid powder 23.9g through acetone recrystallization, yield 72%.
The present embodiment selects 40g (0.11mol) prednisone to be that raw material prepares 16a, and 17a-dihydroxyl-21-acetoxyl group-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone fine work 23.9g (0.057mol), total molar yield is 53.7%.
Embodiment 5
1) in the reaction flask of a 500ml drying; add 70g raw material prednisone (0.2mol), 140ml ethyl acetate, 140ml acetic anhydride, 0.35g tosic acid, load onto reflux condensing tube, stir under nitrogen protection and heat up and temperature control 70 DEG C reaction 2.5h.TLC detection reaction terminates rear cool to room temperature, boil off ethyl acetate, then add 200ml water washing, filter, after filter cake cryodrying, obtain crude product, product obtains white solid powder A (17a through separating-purifying, 21-diacetoxy-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone) 76.9g, yield 87%.
2) by 76.9g intermediate A (0.17mol), 200ml DMF, 76.9g Potassium ethanoate, add in there-necked flask, be heated with stirring to 100 DEG C of reaction 5h, TLC tracing detection and be reacted to completely.Be down to room temperature, reaction solution slowly poured in 200ml frozen water under stirring, separate out off-white powder.Filter, filter cake 200ml × 2 water washings, obtain crude product after drying, product obtains off-white powder B (21-acetoxyl group-Isosorbide-5-Nitrae, 16-pregnen diethylene-3,11,20-triketone) 59.4g through separating-purifying, yield 91.5%.
3) 59.4g intermediate B (0.15mol) added in there-necked flask, add 250ml acetone, 13.8g formic acid (0.3mol), stir, be cooled to less than 0 DEG C.Add the acetone soln 300ml of 23.7g potassium permanganate, after HPLC detection 30min has reacted, 18.9g sodium bisulfite (0.15mol) added in reaction solution, stirs, filter, filter cake 3 × 50ml washing with acetone, merging filtrate.After filtrate concentrates out acetone, add 200ml elutriation brilliant, leave standstill, suction filtration, dry light yellow solid C (16a, 17a-dihydroxyl-21-acetoxyl group-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone) product obtains white solid powder 47.6g through acetone recrystallization, yield 76.3%.
The present embodiment selects 70g (0.2mol) prednisone to be that raw material prepares 16a, and 17a-dihydroxyl-21-acetoxyl group-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone fine work 47.6g (0.114mol), total molar yield is 57.2%.
Claims (5)
1. be the method for starting raw material synthesising target compound with prednisone, comprise the following steps:
(1) prednisone and acetic anhydride are carried out esterification, obtain intermediate 17a, 21-diacetoxy-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone.
(2) salt of above-mentioned obtained intermediate 17a, 21-diacetoxy-Isosorbide-5-Nitrae-pregnen diethylene-3,11,20-triketone alkali or alkalescence is carried out degreasing reaction, obtain intermediate 21-acetoxyl group-Isosorbide-5-Nitrae, 16-pregnant steroid triolefin-3,11,20-triketone.
(3) by above-mentioned obtained intermediate 21-acetoxyl group-Isosorbide-5-Nitrae, the pregnant steroid triolefin-3,11 of 16-, 20-triketone uses potassium permanganate oxidation in an acidic solution, obtains target product 16a, 17a-dihydroxyl-21-acetoxyl group-1,4-pregnen diethylene-3,11,20-triketone.
2. preparation method as claimed in claim 1, is characterized in that: the esterification described in step (1) completes under the catalytic condition of tosic acid.
3. preparation method as claimed in claim 1 or 2, is characterized in that: the temperature of the esterification described in step (1) is 65-80 DEG C.
4. the preparation method as described in any one of claim 1 or 2, is characterized in that: the degreasing temperature of reaction described in step (2) is 90-105 DEG C.
5. as claimed in claim 1 or 2, it is characterized in that: the solvent of the oxidizing reaction described in step (3) is the mixing solutions of acetone and water, acidic solution is any one of formic acid or acetic acid, and temperature is-5 DEG C-0 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410480127.8A CN104447930A (en) | 2014-09-19 | 2014-09-19 | Preparation method of 16a,17a-dyhydroxyl-21-acetoxyl-1,4-pregnene diene-3,11,20-triketone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410480127.8A CN104447930A (en) | 2014-09-19 | 2014-09-19 | Preparation method of 16a,17a-dyhydroxyl-21-acetoxyl-1,4-pregnene diene-3,11,20-triketone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104447930A true CN104447930A (en) | 2015-03-25 |
Family
ID=52894739
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410480127.8A Pending CN104447930A (en) | 2014-09-19 | 2014-09-19 | Preparation method of 16a,17a-dyhydroxyl-21-acetoxyl-1,4-pregnene diene-3,11,20-triketone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104447930A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105061549A (en) * | 2015-08-20 | 2015-11-18 | 上海信谊百路达药业有限公司 | Budesonide preparing method |
| CN109575095A (en) * | 2019-01-20 | 2019-04-05 | 湖南科瑞生物制药股份有限公司 | A kind of preparation method of 16a- hydroxacetic acid prednisolone |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3133940A (en) * | 1956-04-10 | 1964-05-19 | Glaxo Group Ltd | Process for the separation of delta-1, 4-3-keto steroid compounds from mixtures thereof with other 3-keto steroids |
| CN101863952A (en) * | 2010-04-30 | 2010-10-20 | 湖北葛店人福药业有限责任公司 | Preparation method of budesonide |
| CN102146113A (en) * | 2010-02-08 | 2011-08-10 | 仙居县力天化工有限公司 | Method for synthesizing 16 alpha-hydroxy prednisolone |
-
2014
- 2014-09-19 CN CN201410480127.8A patent/CN104447930A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3133940A (en) * | 1956-04-10 | 1964-05-19 | Glaxo Group Ltd | Process for the separation of delta-1, 4-3-keto steroid compounds from mixtures thereof with other 3-keto steroids |
| CN102146113A (en) * | 2010-02-08 | 2011-08-10 | 仙居县力天化工有限公司 | Method for synthesizing 16 alpha-hydroxy prednisolone |
| CN101863952A (en) * | 2010-04-30 | 2010-10-20 | 湖北葛店人福药业有限责任公司 | Preparation method of budesonide |
Non-Patent Citations (2)
| Title |
|---|
| DEREK H.R.BARTON等: "Electrophilic fluorination of some steroidal α,β-unsaturated Ketones", 《PERKIN TRANSACTIONS 1:ORGANIC AND BIO-ORGANIC CHEMISTRY》 * |
| GARDI, RINALDO等: "Derivatives from corticosteroid side-chain condensation. III. Preparation and reactions of 17-monoesters", 《GAZZETTA CHIMICA ITALIANA》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105061549A (en) * | 2015-08-20 | 2015-11-18 | 上海信谊百路达药业有限公司 | Budesonide preparing method |
| CN109575095A (en) * | 2019-01-20 | 2019-04-05 | 湖南科瑞生物制药股份有限公司 | A kind of preparation method of 16a- hydroxacetic acid prednisolone |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106279340B (en) | A method of synthesis momestasone furoate or its monohydrate | |
| CN104910231B (en) | A kind of synthetic method of 25-hydroxyl-7-DHC | |
| CN103304512A (en) | Preparation method for febuxostat | |
| CN106256824A (en) | A kind of preparation method of high-purity De Lasha star meglumine salt | |
| CN112079848A (en) | Synthesis method of baroxavir key intermediate | |
| CN109851653A (en) | The preparation method of 16 alpha-hydroxy prednisonlones | |
| CN114874277A (en) | Synthesis method of cholesterol | |
| CN102731605B (en) | A kind of purification process of Abiraterone acetate | |
| CN104761552B (en) | A kind of processing method of ganciclovir condensation substance isomer | |
| CN104447930A (en) | Preparation method of 16a,17a-dyhydroxyl-21-acetoxyl-1,4-pregnene diene-3,11,20-triketone | |
| CN105254693A (en) | Synthetic method for tildipirosin | |
| CN114605410A (en) | Preparation method of non-neferitone bulk drug | |
| CN101607971A (en) | 9-[2-(diethoxy phosphonium mesitoyl methoxyl group) ethyl] synthetic method of VITAMIN B4 | |
| CN105566336A (en) | Novel method for removing methyl impurity in preparation of asenapine | |
| CN109438334A (en) | A kind of synthetic method of Du Lutewei intermediate | |
| CN105693803A (en) | Method for preparing progesterone | |
| CN104447509B (en) | A kind of preparation technology of tirofiban hydrochloride | |
| CN107188888A (en) | A kind of methanesulfonic acid for preparing steps the auspicious method for Buddhist nun | |
| CN106831759A (en) | The preparation method of Pabuk former times profit cloth and its intermediate | |
| CN104892609A (en) | Linagliptin intermediate, preparation method and applications thereof | |
| CN109748860A (en) | A kind of synthetic method of 2,5- dibromo pyridine | |
| CN108033892A (en) | A kind of preparation method of N- alkyl iminodiacetics acid | |
| CN100368375C (en) | 3- alkoxy -4-carbalkoxyphenylacetate and 3-alkoxy-4-carbalkoxyphenylacetic acid synthesis method | |
| CN103351346A (en) | Preparation method of impurity HP1 in bendamustine hydrochloride | |
| CN103387595B (en) | A kind of preparation method of prednisolone |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20150325 |