CN102452991A - Synthetic technology of hapten 3-(3-chlorine-propyl)diazepam - Google Patents
Synthetic technology of hapten 3-(3-chlorine-propyl)diazepam Download PDFInfo
- Publication number
- CN102452991A CN102452991A CN2010105106945A CN201010510694A CN102452991A CN 102452991 A CN102452991 A CN 102452991A CN 2010105106945 A CN2010105106945 A CN 2010105106945A CN 201010510694 A CN201010510694 A CN 201010510694A CN 102452991 A CN102452991 A CN 102452991A
- Authority
- CN
- China
- Prior art keywords
- reaction
- diazepam
- hapten
- chlorine
- propyl
- 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
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a synthetic technology of halogenated derivatives of hapten diazepam, and concretely relates to a synthetic technology of hapten 3-(3-chlorine-propyl)diazepam. The synthetic technology of hapten 3-(3-chlorine-propyl)diazepam provided in the invention is simple to operate, and hapten 3-(3-chlorine-propyl)diazepam can be reacted with protein molecules. A technical scheme adopted in the invention is characterized in that the synthetic technology comprises the following steps: 1, adjusting amounts of acetone and liquid nitrogen to cool a reaction system to -20 - -60DEG C, adding 8-9mmol of 1-chlorine-3-bromopropane, heating the reaction system to 5-10DEG C, stirring for 1.5-2.5h to obtain a yellow liquid, and adding a saturated sodium chloride solution to terminate the reaction; and 2, pouring the obtained reaction solution into a separating funnel, allowing it to stand for layering, separating the organic phase, carrying out reduced pressure distillation to remove excess THF (tetrahydrofuran) to obtain a crude solid product, carrying out column chromatography, and separating to obtain a white solid product (hapten 3-(3-chlorine-propyl)diazepam).
Description
Technical field:
The present invention relates to the synthesis technique of the stable halo derivatives of a kind of haptin, more particularly, relate to the stabile synthesis technique of haptin 3-(3-chloro-propyl group).
Background technology:
Stable, promptly diazepam belongs to benzodiazepine, and anxiety, tranquilizing soporific, effect such as anticonvulsion, of flaccid muscles and stable are arranged, and is one of the widest sedative hypnotic of present clinical application.Stable type of poisoning or dead case due to owing to eat by mistake, commit suiside or poison happen occasionally; After organic solvents such as domestic and international at present main use ether extract from body fluid or internal organs, adopt vapor-phase chromatography, HPLC or TLCS etc. to detect to stable.These methods are had relatively high expectations to sample, and used instrument is expensive, are difficult to carry out in lack of money and skills personnel's basic unit.
Adopt immunological technique, use the specific anti body tag, can directly be used for detecting, do not need sample is carried out special processing through antigen, antibodies specific reaction, highly sensitive.Because stable itself do not have immunogenicity for small-molecule substance, can not induce antibody to produce, need be connected to form hapten carrier complex with macromolecular substance can stimulate body to produce specific antibody.But do not contain in the stable molecule can with the carboxyl of protein molecule generation acylation reaction or diazotization reaction (COOH) or amino (NH
2).
Summary of the invention:
The present invention is exactly to the problems referred to above, and a kind of simple to operate, stabile synthesis technique of haptin 3-(3-chloro-propyl group) that can react with protein molecule is provided.
In order to realize above-mentioned purpose of the present invention, the present invention adopts following technical scheme, and process step is:
There-necked flask taken out with nitrogen wash 5 times, make and be nitrogen in the device; Get anhydrous diisopropylamine of 1.0～1.2ml and the anhydrous THF of 20ml with the dry injection device respectively, add reaction flask, in acetone solution-liquid nitrogen bath, temperature in the reaction flask is cooled to-60～-100 ℃ from injection port; Extract 5～6mL butyllithium with the dry injection device, join in the reaction flask, in 20～25min, make temperature rise to 20～25 ℃ behind the stirring 10min, get red liquid; Cool to-60～-100 ℃ once more, add and stabilize in reaction flask, stir, make temperature in 20～25min, rise to 20～25 ℃, continue to stir 15min by-60～-100 ℃ with the anhydrous THF dissolved of 20mL 6.6～8.8mmol; Regulate the consumption of acetone, liquid nitrogen, the temperature of reaction system is reduced to-20～-60 ℃, add 1-chloro-3-N-PROPYLE BROMIDE 8～9mmol, temperature rises to 5～10 ℃, stirs 1.5～2.5h, gets yellow liquid, adds saturated NaCl solution, termination reaction; Reaction solution is poured in the separating funnel, and static layering is separated organic phase, remove excessive THF under reduced pressure and obtain solid crude product, through column chromatography, separate white solid product.
Reaction equation is:
Beneficial effect of the present invention:
1. step of the present invention is few, reaction conditions is gentle;
2. synthetic 3-of the present invention (3-chloro-propyl group) stable can with the protein coupling;
3. productive rate of the present invention is 61.06%.
Embodiment:
Process step of the present invention is:
There-necked flask taken out with nitrogen wash 5 times, make and be nitrogen in the device; Get anhydrous diisopropylamine of 1.0～1.2ml and the anhydrous THF of 20ml with the dry injection device respectively, add reaction flask, in acetone solution-liquid nitrogen bath, temperature in the reaction flask is cooled to-60～-100 ℃ from injection port; Extract 5～6mL butyllithium with the dry injection device, join in the reaction flask, in 20～25min, make temperature rise to 20～25 ℃ behind the stirring 10min, get red liquid; Cool to-60～-100 ℃ once more, add and stabilize in reaction flask, stir, make temperature in 20～25min, rise to 20～25 ℃, continue to stir 15min by-60～-100 ℃ with the anhydrous THF dissolved of 20mL 6.6～8.8mmol; Regulate the consumption of acetone, liquid nitrogen, the temperature of reaction system is reduced to-20～-60 ℃, add 1-chloro-3-N-PROPYLE BROMIDE 8～9mmol, temperature rises to 5～10 ℃, stirs 1.5～2.5h, gets yellow liquid, adds saturated NaCl solution, termination reaction; Reaction solution is poured in the separating funnel, and static layering is separated organic phase, remove excessive THF under reduced pressure and obtain solid crude product, through column chromatography, separate white solid product.
Reaction equation is:
As a kind of preferred version, process step of the present invention is: temperature of reaction is 10 ℃, and the reaction times is 120min.
End product of the present invention has obtained the affirmation of infrared spectrum and nuclear magnetic spectrogram.
IR result's demonstration, 3010,1607,1575,1566cm
-1It is respectively the absorption of hydrocarbon, the carbon-carbon double bond and the carbon-to-nitrogen double bon of phenyl ring; 2985,2900,2878cm
-1It is saturated hydrocarbon absorption; 1687cm
-1It is the absorption of carbonyl; 788,700cm
-1It is the absorption of carbon chlorine key.In the data of 1HNMR, (m 8H) has explained two phenyl ring in the target compound to δ 7.59～7.23; (t 2H) is-CH δ 3.59
2Cl; (t is to be connected-CH-with nitrogen with carbonyl 1H) to δ 3.54～3.50; (s 3H) is N-CH to δ 3.38
3(m 2H) is in the molecule-CH δ 2.42～2.27
2-CH
2-CH
2-; 2.25～1.87 (q 2H) is in the molecule-CH-CH
2-CH
2-CH
2-Cl.
Claims (2)
1. the stabile synthesis technique of haptin 3-(3-chloro-propyl group) is characterized in that the present invention adopts following technical scheme, and process step is:
There-necked flask taken out with nitrogen wash 5 times, make and be nitrogen in the device; Get anhydrous diisopropylamine of 1.0～1.2ml and the anhydrous THF of 20ml with the dry injection device respectively, add reaction flask, in acetone solution-liquid nitrogen bath, temperature in the reaction flask is cooled to-60～-100 ℃ from injection port; Extract 5～6mL butyllithium with the dry injection device, join in the reaction flask, in 20～25min, make temperature rise to 20～25 ℃ behind the stirring 10min, get red liquid; Cool to-60～-100 ℃ once more, add and stabilize in reaction flask, stir, make temperature in 20～25min, rise to 20～25 ℃, continue to stir 15min by-60～-100 ℃ with the anhydrous THF dissolved of 20mL 6.6～8.8mmol; Regulate the consumption of acetone, liquid nitrogen, the temperature of reaction system is reduced to-20～-60 ℃, add 1-chloro-3-N-PROPYLE BROMIDE 8～9mmol, temperature rises to 5～10 ℃, stirs 1.5～2.5h, gets yellow liquid, adds saturated NaCl solution, termination reaction; Reaction solution is poured in the separating funnel, and static layering is separated organic phase, remove excessive THF under reduced pressure and obtain solid crude product, through column chromatography, separate white solid product.
Reaction equation is:
2. the stabile synthesis technique of haptin 3-according to claim 1 (3-chloro-propyl group), it is characterized in that process step of the present invention is: temperature of reaction is 10 ℃, the reaction times is 120min.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105106945A CN102452991A (en) | 2010-10-19 | 2010-10-19 | Synthetic technology of hapten 3-(3-chlorine-propyl)diazepam |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105106945A CN102452991A (en) | 2010-10-19 | 2010-10-19 | Synthetic technology of hapten 3-(3-chlorine-propyl)diazepam |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102452991A true CN102452991A (en) | 2012-05-16 |
Family
ID=46036719
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010105106945A Pending CN102452991A (en) | 2010-10-19 | 2010-10-19 | Synthetic technology of hapten 3-(3-chlorine-propyl)diazepam |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102452991A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102830222A (en) * | 2012-09-20 | 2012-12-19 | 成都斯马特科技有限公司 | Method for preparing solid granular biochemical reagent |
-
2010
- 2010-10-19 CN CN2010105106945A patent/CN102452991A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102830222A (en) * | 2012-09-20 | 2012-12-19 | 成都斯马特科技有限公司 | Method for preparing solid granular biochemical reagent |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Chen et al. | Highly Enantioselective Michael Addition of Cyclic 1, 3‐Dicarbonyl Compounds to β, γ‐Unsaturated α‐Keto Esters | |
| BR112018008877B1 (en) | RET-INHIBITOR COMPOUNDS, PHARMACEUTICAL COMPOSITION AND USES OF SUCH COMPOUNDS | |
| CN104945322B (en) | Detect the compound and preparation method thereof of tumor hypoxia | |
| Arnoldi et al. | New colored compounds from the Maillard reaction between xylose and lysine | |
| Wang et al. | Chemoselective synthesis of polycyclic spiroindolines and polysubstituted pyrroles via the domino reaction of 2-isocyanoethylindoles | |
| Diethelm et al. | Mechanistic insight into the spirocyclopropane isoxazolidine ring contraction | |
| CN103864774B (en) | A kind of preparation method of Lurasidone | |
| CN104807924A (en) | Method for detecting specific impurities in ornithine aspartate raw material and preparation thereof | |
| Nandi et al. | Direct Synthesis of N‐Acyl Sulfonimidamides and N‐Sulfonimidoyl Amidines from Sulfonimidoyl Azides | |
| Bogolubsky et al. | A one-pot parallel reductive amination of aldehydes with heteroaromatic amines | |
| Jadhav et al. | Pyrido [1, 2‐a] pyrimidin‐4‐ones: Ligand‐based Design, Synthesis, and Evaluation as an Anti‐inflammatory Agent | |
| CN101671345B (en) | Curcumol hapten and artificial antigen as well as preparation method thereof | |
| CN102964287B (en) | Synthesis method of 3-(4-chlorobutyl)-5-cyanoindole | |
| CN103030600A (en) | Synthesis process of hapten 3-(3-chlorine-propyl) diazepam | |
| CN102452991A (en) | Synthetic technology of hapten 3-(3-chlorine-propyl)diazepam | |
| CN103965093A (en) | 2-perfluoroalkyl indole compound as well as preparation and application thereof | |
| Amaike et al. | Direct C7 Functionalization of Tryptophan. Synthesis of Methyl (S)-2-((tert-Butoxycarbonyl) amino)-3-(7-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)-1H-indol-3-yl) propanoate | |
| CN102584835A (en) | Spiral heterocyclic compound containing indole structure and method for preparing same | |
| CN104478809B (en) | A kind of levosimendan impurity and preparation thereof and detection method | |
| Wang et al. | Direct Introduction of− OCD3 into the Hantzsch Pyrrole Synthesis via Multicomponent Cascade Cyclization: Synthesis of Fully Substituted Pyrrole Derivatives | |
| CN107382814B (en) | It is a kind of based on small-molecule fluorescent probe and its preparation method and application | |
| CN104672125B (en) | A kind of indoles hydrazone compound | |
| CN108976179B (en) | Preparation method for preparing deuterated compound by using deuterium source as deuterium source | |
| Hu et al. | Visible-light induced green synthesis of γ-deuterated carbonyl compounds | |
| Hesk et al. | Synthesis of pentamidine labelled with tritium and carbon‐14 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| DD01 | Delivery of document by public notice | ||
| DD01 | Delivery of document by public notice |
Addressee: Dan Qiang Document name: Notification that Application Deemed to be Withdrawn |
|
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120516 |