CN108659090A - A kind of preparation method of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds - Google Patents
A kind of preparation method of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds Download PDFInfo
- Publication number
- CN108659090A CN108659090A CN201710209514.1A CN201710209514A CN108659090A CN 108659090 A CN108659090 A CN 108659090A CN 201710209514 A CN201710209514 A CN 201710209514A CN 108659090 A CN108659090 A CN 108659090A
- Authority
- CN
- China
- Prior art keywords
- esters
- chloromethane
- preparation
- steroidal compounds
- added
- 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
- OQROBLSTZFMSKR-NWBZAITASA-N C[C@H](CC(C(C[C@@H](C([C@]1(C)C=C2)=CC2=O)F)[C@@]11F)[C@]2(C)C[C@@H]1[O]=C)[C@@]2(C(SC)=O)O Chemical compound C[C@H](CC(C(C[C@@H](C([C@]1(C)C=C2)=CC2=O)F)[C@@]11F)[C@]2(C)C[C@@H]1[O]=C)[C@@]2(C(SC)=O)O OQROBLSTZFMSKR-NWBZAITASA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/001—Oxiranes
- C07J71/0015—Oxiranes at position 9(11)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/0026—Oxygen-containing hetero ring cyclic ketals
- C07J71/0031—Oxygen-containing hetero ring cyclic ketals at positions 16, 17
Abstract
The invention discloses a kind of preparation methods of 17 β thiocarboxylic acids chloromethane esters steroidal compounds, under alkaline condition, using dichloromethane as chloromethylation reagents, prepare 17 β thiocarboxylic acid chloromethane esters steroidal compounds.This process conditions is mild, and agents useful for same is easy to get, and simplifies operating procedure, cost reduction, and yield improves, more environmentally-friendly, is suitble to industrialized production.
Description
Technical field
The present invention relates to a kind of preparation methods of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds, belong to steroidal synthesis skill
Art field.
Background technology
17 β-thiocarboxylic acid chloromethane esters steroidal compounds are a kind of important steroid drugs or pharmaceutical intermediate structure, are used
Way is extensively.
Chloromethylation reagents mainly wrap used in the preparation of the 17 β-thiocarboxylic acid chloromethane esters steroidal compounds of document report
Include chloroiodomethane, chlorobromomethane etc., patent CN101125875, US20090275767 and document " Synthesis and
biological properties of novel glucocorticoid androstene C-17furoate esters”、
" Organic Preparations and Procedures International, 2008, Volume:40,Issue:6,
Using chlorobromomethane as methylating reagent in 566-571 ", chlorobromomethane has irritation, is easy to be damaged by human body sucking, right
Environment is also harmful, can be polluted to water body and soil, is easy to accumulate in organism；Patent WO2004039827, WO
2008115069 use chloroiodomethane as methylating reagent, and the reagent purity is low, and expensive；Patent CN103249716 makes
(chloromethyl) (phenyl) (2,3,4,5- tetramethylphenyls) sulfonium fluoroform sulphonate is used to prepare 17 β-sulphur as chloromethylation reagents
For carboxylic acid chloromethane esters steroidal compounds, yield 90% or so, still (chloromethyl) (phenyl) (2,3,4,5- tetramethylphenyl)
Sulfonium fluoroform sulphonate prepares difficulty, is not suitable for mass producing.
To sum up, at present these chloromethylation reagents there are it is expensive, be not easy to obtain, so that reaction system is generated more miscellaneous
Therefore the deficiencies of matter, cumbersome post-processing, develops a kind of new 17 β-thiocarboxylic acid chloromethane esters steroidal compounds preparation processes tool
It is significant.
Invention content
The object of the present invention is to provide a kind of 17 β-thiocarboxylic acid chloromethane esters sterides compounds at low cost, production efficiency is high
The preparation method of object.Basic catalyst is added in chloromethylation in we, using dichloromethane as chloromethylation reagents
17 β-thiocarboxylic acid chloromethane esters steroidal compounds are generated, cost is greatly reduced, reduces the generation of impurity, simplify the later stage
Purification procedures, and it is more environmentally-friendly, it is suitble to large-scale production.
A kind of preparation method of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds, it is characterised in that steps are as follows：
Under alkaline condition, compound A is reacted with dichloromethane, obtains 17 β-thiocarboxylic acid chloromethane esters sterides compounds
Object B
For singly-bound or double bond
R1、R2、R3、R4、R5Independently of one another selection and wherein：
R1=α-OH, β-OH ,-H or=O
R2=α-Cl, α-Br, α-F or α-H
Or R1And R29 β, 11 beta epoxides can be formed together
R3=F, Cl, CH3、H
R4=-H, α-OH, α-OCOR6, R6For alkyl, alkoxy or the furyl within six carbon
R5=-H, α-OH, α-CH3、β-CH3
Or R4And R5The part of part or Formula II with Formulas I can be formed together：
For wherein X and Y independently selected from hydrogen or alkyl, condition is when one of X or Y are hydrogen, the other is alkyl；
Work as R2When=α-Br or α-F, R1=β-OH
Work as R1For=O when, R2=α-H.
A kind of preparation method of the 17 β-thiocarboxylic acids chloromethane esters steroidal compounds, it is characterised in that：
For singly-bound or double bond
R1=α-OH, β-OH
R2=Cl, Br, F
R3=F, Cl
R4=α-OCOR6, R6For the alkyl or furyl within three carbon
R5=α-CH3、β-CH3
Work as R2When=α-Br or α-F, R1=β-OH.
A kind of preparation method of the 17 β-thiocarboxylic acids chloromethane esters steroidal compounds, it is characterised in that：
R1=β-OH
R2=F
R3=F
R4=α-OCOR6, R6For the alkyl or furyl of two carbon
R5=α-CH3。
A kind of preparation method of the 17 β-thiocarboxylic acids chloromethane esters steroidal compounds, it is characterised in that：Alkali used
The one kind of type in inorganic base, alkyl amine, secondary amine, aromatic amine.
A kind of preparation method of the 17 β-thiocarboxylic acids chloromethane esters steroidal compounds, it is characterised in that：The nothing
Machine alkali is selected from sodium hydroxide, potassium hydroxide, lithium hydroxide, cesium carbonate, potassium carbonate, sodium carbonate, sodium bicarbonate, saleratus, Asia
One kind in sodium sulphate；The one kind of the alkyl amine in triethylamine, Trimethylamine；The secondary amine be selected from diethylamide,
One kind in dimethyl amine；The one kind of the aromatic amine in 4-dimethylaminopyridine, pyridine, quinoline.
A kind of preparation method of the 17 β-thiocarboxylic acids chloromethane esters steroidal compounds, it is characterised in that：Reactant
Cosolvent is added in system, the cosolvent is selected from dimethylformamide, dimethylacetylamide, hydroxy propyl methacrylate, first
It is one or more in alcohol, hexamethyl phosphoramide.
A kind of preparation method of the 17 β-thiocarboxylic acids chloromethane esters steroidal compounds, it is characterised in that：Reactant
Add surfactant in system, the surfactant in 4-butyl ammonium hydrogen sulfate, benzyltriethylammoinium chloride one
Kind.
A kind of preparation method of the 17 β-thiocarboxylic acids chloromethane esters steroidal compounds, it is characterised in that：With quality
Than calculating, the rate of charge of the surfactant and compound A are 0.05-0.1：1.
A kind of preparation method of the 17 β-thiocarboxylic acids chloromethane esters steroidal compounds, it is characterised in that：Reactant
Auxiliary agent, the one kind of the auxiliary agent in sodium iodide, sodium bromide, preferably sodium iodide are added in system.
A kind of preparation method of the 17 β-thiocarboxylic acids chloromethane esters steroidal compounds, it is characterised in that：With quality
Than calculating, the rate of charge of the auxiliary agent and compound A are 0.05-0.1：1.
It is found through experiment that the yield and content of final products can be improved after sodium iodide is added in reaction system.
Specific implementation mode
Below will by embodiment, the invention will be further described, these description be not to the content of present invention make into
The restriction of one step.Related technical personnel should be understood that equivalent replacement made by the technical characteristic to the present invention, or be correspondingly improved,
It still falls within protection scope of the present invention.
Embodiment 1 is with compound 1 for starting material prepare compound 2
Embodiment 1-1
6g saleratus and 150ml methanol are added into 500ml reaction bulbs, stirs evenly at room temperature, adds into reaction bulb
Enter 30.0g compounds 1 and dichloromethane 60ml, be stirred to react 1 hour, TLC monitoring reaction process to reactions terminate, by reaction solution
It is diluted in 1500ml water, stirring is filtered after 1 hour, drying, and absolute ethyl alcohol recrystallization is added, filters, and 26.8gization is obtained after dry
Close object 2, mass yield 89.2%, purity 95.2%.
Embodiment 1-2
6g potassium carbonate and 150ml dimethylformamides are added into 500ml reaction bulbs, stirs evenly at room temperature, to reaction
30.0g compounds 1 are added in bottle, stirring is added dichloromethane 60ml and reacts 1.5 hours, and TLC monitors reaction process to reacting knot
Reaction solution is diluted in 1500ml water by beam, and stirring is filtered after 1 hour, dry, and absolute ethyl alcohol recrystallization is added, filters, dry
26.5g compounds 2, mass yield 88.3%, purity 95.3% are obtained afterwards.
Embodiment 1-3
6g lithium hydroxides and 210ml dichloromethane are added into 500ml reaction bulbs, stirs evenly at room temperature, to reaction bulb
Middle addition 30.0g compounds 1 and sodium iodide 2.6g, are stirred to react 2 hours, and TLC monitoring reaction process to reactions terminate, dichloromethane
Alkane layer is washed once with 300ml, and anhydrous sodium sulfate is added and dries 1 hour, filters, concentration is evaporated dichloromethane, and anhydrous second is added
Alcohol recrystallizes, and filters, and 28.9g compounds 2, mass yield 96.4%, purity 99.2% are obtained after dry.
Embodiment 1-4
6g cesium carbonates and 210ml dichloromethane are added into 500ml reaction bulbs, stirs evenly at room temperature, into reaction bulb
30.0g compounds 1 and benzyltriethylammoinium chloride 2.5g is added, is stirred to react 2.5 hours, TLC monitors reaction process to reaction
Terminating, dichloromethane layer is washed once with 300ml, and anhydrous sodium sulfate is added and dries 1 hour, filters, and concentration is evaporated dichloromethane,
Absolute ethyl alcohol recrystallization is added, filters, 24.9g compounds 2, mass yield 83.0%, purity 96.2% are obtained after dry.
Embodiment 1-5
6g sodium sulfites and 150ml hexamethyl phosphoramides are added into 500ml reaction bulbs, stirs evenly at room temperature, to anti-
It answers and 30.0g compounds 1 is added in bottle, stirring is added 60ml dichloromethane and reacts 2 hours, and TLC monitors reaction process to reacting knot
Reaction solution is diluted in 1500ml water by beam, and stirring is filtered after 1 hour, dry, and absolute ethyl alcohol recrystallization is added, filters, dry
24.8g compounds 2, mass yield 82.8%, purity 96.1% are obtained afterwards.
Embodiment 1-6
6ml triethylamines and 210ml dichloromethane are added into 500ml reaction bulbs, stirs evenly at room temperature, into reaction bulb
30.0g compounds 1 are added, stirs and 4-butyl ammonium hydrogen sulfate 2.0g reactions 2.5 hours is added, TLC monitors reaction process to reaction
Terminating, dichloromethane layer is washed once with 300ml, and anhydrous sodium sulfate is added and dries 1 hour, filters, and concentration is evaporated dichloromethane,
Absolute ethyl alcohol recrystallization is added, filters, 24.8g compounds 2, mass yield 82.5%, purity 96.6% are obtained after dry.
Embodiment 1-7
6g sodium bicarbonates and 210ml dichloromethane are added into 500ml reaction bulbs, stirs evenly at room temperature, to reaction bulb
Middle addition 30.0g compounds 1, stirring are added sodium bromide 3g and react 2 hours, and TLC monitoring reaction process to reactions terminate, dichloromethane
Alkane layer is washed once with 300ml, and anhydrous sodium sulfate is added and dries 1 hour, filters, concentration is evaporated dichloromethane, and anhydrous second is added
Alcohol recrystallizes, and filters, and 24.3g compounds 2, mass yield 80.9%, purity 96.3% are obtained after dry.
Embodiment 1-8
6ml pyridines and 210ml dichloromethane are added into 500ml reaction bulbs, stirs evenly at room temperature, adds into reaction bulb
Enter 30.0g compounds 1, be stirred to react 3 hours, TLC monitoring reaction process to reactions terminate, and dichloromethane layer is washed with 300ml
Once, anhydrous sodium sulfate is added to dry 1 hour, filters, concentration is evaporated dichloromethane, and absolute ethyl alcohol recrystallization is added, filters, does
24.5g compounds 2, mass yield 81.5%, purity 95.2% are obtained after dry.
Embodiment 2 is with compound 3 for starting material prepare compound 4
6g sodium hydroxides and 150ml dimethylacetylamides are added into 500ml reaction bulbs, stirs evenly at room temperature, to anti-
Addition 30.0g compounds 3 and dichloromethane 60ml in bottle is answered to be stirred to react 1 hour, TLC monitoring reaction process to reactions terminate,
Reaction solution is diluted in 1500ml water, stirring is filtered after 1 hour, dry, and absolute ethyl alcohol recrystallization is added, filters, after dry
Obtain 24.8g compounds 4, mass yield 82.6%, purity 97.1%.
Embodiment 3 is with compound 5 for starting material prepare compound 6
6g potassium carbonate and 150ml methanol are added into 500ml reaction bulbs, stirs evenly, is added into reaction bulb at room temperature
30.0g compounds 5, dichloromethane 60ml is added in stirring and sodium iodide 2.3g reacts 1 hour, and TLC monitors reaction process and extremely reacts
Terminate, reaction solution is diluted in 1500ml water, stirring is filtered after 1 hour, dry, and absolute ethyl alcohol recrystallization is added, filters, does
28.6g compounds 6, mass yield 95.3%, purity 99.5% are obtained after dry.
Embodiment 4 is with compound 7 for starting material prepare compound 8
6ml triethylamines and 150ml hexamethyl phosphoramides are added into 500ml reaction bulbs, stirs evenly at room temperature, to reaction
30.0g compounds 7 are added in bottle, dichloromethane 60ml is added and is stirred to react 1.5 hours, TLC monitors reaction process to reacting knot
Reaction solution is diluted in 1500ml water by beam, and stirring is filtered after 1 hour, dry, and absolute ethyl alcohol recrystallization is added, filters, dry
24.4g compounds 8, mass yield 81.2%, purity 96.2% are obtained afterwards.
Embodiment 5 is with compound 9 for starting material prepare compound 10
6ml pyridines and 150ml hydroxy propyl methacrylates are added into 500ml reaction bulbs, stirs evenly at room temperature, to anti-
It answers and 30.0g compounds 9 is added in bottle, stirring is added dichloromethane 60ml and reacts 1 hour, and TLC monitors reaction process to reacting knot
Reaction solution is diluted in 1500ml water by beam, and stirring is filtered after 1 hour, dry, and absolute ethyl alcohol recrystallization is added, filters, dry
24.2g compounds 10, mass yield 80.6%, purity 95.3% are obtained afterwards.
Embodiment 6 is with compound 11 for starting material prepare compound 12
6ml Trimethylamines and 210ml dichloromethane are added into 500ml reaction bulbs, stirs evenly at room temperature, to reaction bulb
Middle addition 30.0g compounds 11 and sodium bromide 2g are stirred to react 1.5 hours, and TLC monitoring reaction process to reactions terminate, dichloromethane
Alkane layer is washed once with 300ml, and anhydrous sodium sulfate is added and dries 1 hour, filters, concentration is evaporated dichloromethane, and anhydrous second is added
Alcohol recrystallizes, and filters, and 24.5g compounds 12, mass yield 81.6%, purity 96.5% are obtained after dry.
Embodiment 7 is with compound 13 for starting material prepare compound 14
6ml dimethyl amines and 150ml methanol are added into 500ml reaction bulbs, stirs evenly at room temperature, adds into reaction bulb
Enter 30.0g compounds 13, stirring is added dichloromethane 60ml and reacts 2 hours, and TLC monitoring reaction process to reactions terminate, will be anti-
Liquid is answered to be diluted in 1500ml water, stirring is filtered after 1 hour, drying, and absolute ethyl alcohol recrystallization is added, filters, and is obtained after dry
25.0g compounds 14, mass yield 83.4%, purity 95.5%.
Embodiment 8 is with compound 15 for starting material prepare compound 16
6ml dimethyl amines and 210ml dichloromethane are added into 500ml reaction bulbs, stirs evenly at room temperature, to reaction bulb
Middle addition 30.0g compounds 15 and 4-butyl ammonium hydrogen sulfate 2g, are stirred to react 2 hours, TLC monitor reaction process to react knot
Beam, dichloromethane layer are washed once with 300ml, and anhydrous sodium sulfate is added and dries 1 hour, filters, concentration is evaporated dichloromethane, adds
Enter absolute ethyl alcohol recrystallization, filter, 24.3g compounds 16, mass yield 81.0%, purity 95.8% are obtained after dry.
Embodiment 9 is with compound 17 for starting material prepare compound 18
6ml quinoline and 150ml dimethylacetylamides are added into 500ml reaction bulbs, stirs evenly at room temperature, to reaction bulb
Middle addition 30.0g compounds 17, stirring are added dichloromethane 60ml and react 2 hours, and TLC monitoring reaction process to reactions terminate,
Reaction solution is diluted in 1500ml water, stirring is filtered after 1 hour, dry, and absolute ethyl alcohol recrystallization is added, filters, after dry
Obtain 24.6g compounds 18, mass yield 82.0%, purity 96.2%.
Embodiment 10 is with compound 19 for starting material prepare compound 20
6g 4-dimethylaminopyridine and 150ml dimethylformamides are added into 500ml reaction bulbs, stirring is equal at room temperature
It is even, 30.0g compounds 19 are added into reaction bulb and sodium bromide 1.5g is stirred to react 3 hours, TLC monitors reaction process to reaction
Terminate, reaction solution is diluted in 1500ml water, stirring is filtered after 1 hour, dry, and absolute ethyl alcohol recrystallization is added, filters, does
23.4g compounds 20, mass yield 78.0%, purity 95.3% are obtained after dry.
Claims (10)
1. a kind of preparation method of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds, it is characterised in that steps are as follows：
Under alkaline condition, compound A is reacted with dichloromethane, obtains 17 β-thiocarboxylic acid chloromethane esters steroidal compounds B
For singly-bound or double bond
R1、R2、R3、R4、R5Independently of one another selection and wherein：
R1=α-OH, β-OH ,-H or=O
R2=α-Cl, α-Br, α-F or α-H
Or R1And R29 β, 11 beta epoxides can be formed together
R3=F, Cl, CH3、H
R4=-H, α-OH, α-OCOR6, R6For alkyl, alkoxy or the furyl within six carbon
R5=-H, α-OH, α-CH3、β-CH3
Or R4And R5The part of part or Formula II with Formulas I can be formed together：
For wherein X and Y independently selected from hydrogen or alkyl, condition is when one of X or Y are hydrogen, the other is alkyl；
Work as R2When=α-Br or α-F, R1=β-OH
Work as R1For=O when, R2=α-H.
2. a kind of preparation method of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds as described in claim 1, feature exist
In：
For singly-bound or double bond
R1=α-OH, β-OH
R2=Cl, Br, F
R3=F, Cl
R4=α-OCOR6, R6For the alkyl or furyl within three carbon
R5=α-CH3、β-CH3
Work as R2When=α-Br or α-F, R1=β-OH.
3. a kind of preparation method of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds as claimed in claim 2, feature exist
In：
R1=β-OH
R2=F
R3=F
R4=α-OCOR6, R6For the alkyl or furyl of two carbon
R5=α-CH3。
4. a kind of preparation method of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds as described in any one of claims 1-3,
It is characterized in that：
The one kind of alkali type used in inorganic base, alkyl amine, secondary amine, aromatic amine.
5. a kind of preparation method of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds as claimed in claim 4, feature exist
In：
The inorganic base is selected from sodium hydroxide, potassium hydroxide, lithium hydroxide, cesium carbonate, potassium carbonate, sodium carbonate, sodium bicarbonate, carbon
One kind in potassium hydrogen phthalate, sodium sulfite；The one kind of the alkyl amine in triethylamine, Trimethylamine；The secondary amine is selected from
One kind in diethylamide, dimethyl amine；The one kind of the aromatic amine in 4-dimethylaminopyridine, pyridine, quinoline.
6. a kind of preparation method of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds as described in any one of claims 1-3,
It is characterized in that：
Cosolvent is added in reaction system, the cosolvent is selected from dimethylformamide, dimethylacetylamide, methacrylic acid
It is one or more in hydroxypropyl acrylate, methanol, hexamethyl phosphoramide.
7. a kind of preparation method of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds as described in any one of claims 1-3,
It is characterized in that：
Surfactant is added in reaction system, the surfactant is selected from 4-butyl ammonium hydrogen sulfate, benzyl triethyl ammonium chlorine
Change one kind in ammonium.
8. a kind of preparation method of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds as claimed in claim 7, feature exist
In：
It calculates by quality ratio, the rate of charge of the surfactant and compound A are 0.05-0.1：1.
9. a kind of preparation method of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds as described in any one of claims 1-3,
It is characterized in that：
Auxiliary agent, the one kind of the auxiliary agent in sodium iodide, sodium bromide are added in reaction system.
10. a kind of preparation method of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds as claimed in claim 9, feature exist
In：
The auxiliary agent is sodium iodide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710209514.1A CN108659090A (en) | 2017-03-31 | 2017-03-31 | A kind of preparation method of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710209514.1A CN108659090A (en) | 2017-03-31 | 2017-03-31 | A kind of preparation method of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108659090A true CN108659090A (en) | 2018-10-16 |
Family
ID=63784040
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710209514.1A Pending CN108659090A (en) | 2017-03-31 | 2017-03-31 | A kind of preparation method of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108659090A (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003013427A2 (en) * | 2001-08-03 | 2003-02-20 | Smithkline Beecham Corporation | A method for preparing fluticasone derivatives |
| WO2004039827A2 (en) * | 2002-10-30 | 2004-05-13 | Glaxo Group Limited | Glucocorticosteroids having a specific 17a-sidechain useful as antiinflammatory agents |
| CN101125875A (en) * | 2007-08-15 | 2008-02-20 | 湖南甾体化学品有限公司 | Method for preparing fluticasone propionate |
| CN101687904A (en) * | 2007-03-20 | 2010-03-31 | 克拉维斯药物普通股份公司 | Fatty acid ester as the glucocorticosteroid of anti-inflammatory and anticancer agent |
| CN103965150A (en) * | 2014-05-28 | 2014-08-06 | 广州康臣药物研究有限公司 | Scopoletin derivative as well as preparation method and application thereof |
| CN105199422A (en) * | 2015-10-20 | 2015-12-30 | 北京科技大学 | Sulfhydryl group-containing bithiophene benzoindoles dye as well as preparation method and application thereof |
-
2017
- 2017-03-31 CN CN201710209514.1A patent/CN108659090A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003013427A2 (en) * | 2001-08-03 | 2003-02-20 | Smithkline Beecham Corporation | A method for preparing fluticasone derivatives |
| WO2004039827A2 (en) * | 2002-10-30 | 2004-05-13 | Glaxo Group Limited | Glucocorticosteroids having a specific 17a-sidechain useful as antiinflammatory agents |
| CN101687904A (en) * | 2007-03-20 | 2010-03-31 | 克拉维斯药物普通股份公司 | Fatty acid ester as the glucocorticosteroid of anti-inflammatory and anticancer agent |
| CN101125875A (en) * | 2007-08-15 | 2008-02-20 | 湖南甾体化学品有限公司 | Method for preparing fluticasone propionate |
| CN103965150A (en) * | 2014-05-28 | 2014-08-06 | 广州康臣药物研究有限公司 | Scopoletin derivative as well as preparation method and application thereof |
| CN105199422A (en) * | 2015-10-20 | 2015-12-30 | 北京科技大学 | Sulfhydryl group-containing bithiophene benzoindoles dye as well as preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| ANNE BRINKO ET AL.: "Synthesis and inhibitory evaluation of 3-linked imipramines for the exploration of the S2 site of the human serotonin transporter", 《BIOORG. MED. CHEM.》 * |
| VACLAV VANEK ET AL.: "Structure-Activity Study of New Inhibitors of Human Betaine-Homocysteine S-Methyltransferase", 《J. MED. CHEM.》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107629032B (en) | A kind of preparation method of cyclic sulfates | |
| CN101279997A (en) | Novel preparation of budesonide | |
| CN106279340B (en) | A method of synthesis momestasone furoate or its monohydrate | |
| CN108314639A (en) | Compound（E）-3-（1- methylpyrrolidin- 2- bases）Acrylic acid hydrochloride and synthetic method | |
| CN106478528A (en) | The synthesis technique of Favipiravir | |
| CN102395591B (en) | Method for preparing prasugrel | |
| CN107365297A (en) | A kind of Preparation Method And Their Intermediate of the benzyl propionate derivant of 2 methyl 2 ' | |
| CN103772193A (en) | Method for preparing tricyclic derivatives | |
| CN109851653A (en) | The preparation method of 16 alpha-hydroxy prednisonlones | |
| CN104447934A (en) | Method for purifying abiraterone acetate | |
| CN108659090A (en) | A kind of preparation method of 17 β-thiocarboxylic acids chloromethane esters steroidal compounds | |
| CN1325403A (en) | Bile-acid substituted phenyl-alkenoylguanidines, method for the production thereof, use thereof as medicaments or diaymostic agents and medicaments that contain | |
| CN107108649B (en) | Be used to prepare Thienopyrimidine compound novel method and its used in intermediate | |
| CN108659083A (en) | A kind of synthetic method of Loteprednol etabonate | |
| CN108659084A (en) | A kind of preparation method of 17 β-carboxylic acids chloromethane esters steroidal compounds | |
| CN104781231B (en) | The method for preparing travoprost | |
| CN106520892A (en) | 7-amino-3-vinyl cephalosporanic acid preparation method | |
| CN106977571B (en) | A kind of Austria's shellfish cholic acid analogue and its preparation method and application | |
| CN102746207A (en) | Synthesis method of oxiracetam | |
| CN1685818A (en) | Simplified production technology of bisultap | |
| CN106831923A (en) | A kind of preparation method of chenodeoxycholic acid | |
| CN107383066A (en) | A kind of method of latamoxef acid deprotection base | |
| CN103421070A (en) | Improved pregnane alkene compound C21-acetoxylation method | |
| CN110790804B (en) | Synthesis method of steroid cortin 21-hydroxyl side chain | |
| CN102382165A (en) | Preparation method of dutasteride |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information | ||
| CB02 | Change of applicant information |
Address after: 300457 Tianjin Binhai New Area Development Zone West District Xinye nine Street North, Xinhuan West Road East. Applicant after: Tianjin Pharmaceutical Research Institute Co.,Ltd. Address before: 300457 Tianjin Binhai New Area Development Zone West District Xinye nine Street North, Xinhuan West Road East. Applicant before: TIANJIN PHARMACEUTICALS Group Corp. |
|
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20181016 |