CN102329268B - Preparation method for 7-chlorine-5-oxo-2,3,4,5-tetrahydro-1H-1-benzoazepine - Google Patents
Preparation method for 7-chlorine-5-oxo-2,3,4,5-tetrahydro-1H-1-benzoazepine Download PDFInfo
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- CN102329268B CN102329268B CN201110326759.5A CN201110326759A CN102329268B CN 102329268 B CN102329268 B CN 102329268B CN 201110326759 A CN201110326759 A CN 201110326759A CN 102329268 B CN102329268 B CN 102329268B
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Abstract
The invention relates to a preparation method for 7-chlorine-5-oxo-2,3,4,5-tetrahydro-1H-1-benzoazepine. The 7-chlorine-5-oxo-2,3,4,5-tetrahydro-1H-1-benzoazepine is an important intermediate for preparing arginine pitressin V2 receptor antagonist Tolvaptan. In the preparation method, the target product 7-chlorine-5-oxo-2,3,4,5-tetrahydro-1H-1-benzoazepine is prepared by removing tosyl and carbalkoxy from 7-chlorine-5-oxo-4-carbalkoxy-1-tosyl-2,3,4,5-tetrahydro-1-benzoazepine serving as a raw material under the action of sulfuric acid and by a 'one-pot method'. The sulfuric acid is used for performing 'one-pot method' reaction, so reaction steps are reduced and reaction time is greatly shortened. The preparation method has the advantages of simpleness and convenience for operation, equipment and cost saving, simpleness and practicability in separation and purification, short reaction time, high yield and high product purity and is applicable to industrialized production.
Description
Technical field
The invention belongs to technical field of pharmaceutical chemistry, relate in particular to a kind of novel arginine vasopressin V
2the chloro-5-of receptor antagonist tolvaptan intermediate 7-oxo-2, the preparation method of 3,4,5-tetrahydrochysene-1H-1-benzazepine.
Background technology
The chloro-5-of 7-oxo-2,3,4,5-tetrahydrochysene-1H-1-benzazepine is the important intermediate of synthetic drugs tolvaptan.Tolvaptan is a kind of non-peptide class selectivity V that Japan large tomb (Otsuka) company develops
2receptor antagonist, can reduce body fluid and load and do not affect electrolyte balance and renal function, is a kind of effective diuretic(s), is applicable to the treatment of the diseases such as hyponatremia.
The preparation of this product is existing bibliographical information both at home and abroad, as document Chinese Journal of Pharmaceuticals .2009, and 40 (9): following synthetic method is provided in 648-650:
There is obvious defect in this method, by the chloro-5-oxo-4-carbalkoxy-1-of 7-p-toluenesulfonyl-2,3; 4; the synthetic chloro-5-of 7-of 5-tetrahydrochysene-1-benzazepine oxo-2,3,4; in the process of 5-tetrahydrochysene-1H-1-benzazepine; reaction is in two steps carried out, and slow by hydrochloric acid reaction speed, productive rate is low and impurity is many; the PPA toughness that final step is used is high, and easily the moisture absorption and cost are higher.In addition, in Chinese patent CN101273017A, the synthetic chloro-5-of 7-of final step oxo-2,3,4,5-tetrahydrochysene-1H-1-changes PPA into the vitriol oil during benzazepine, but has passed through two-step reaction, and reaction scheme is long, yield is low, and cost is high, is not suitable for suitability for industrialized production.
Summary of the invention
The present invention is directed to the deficiencies in the prior art, provide the chloro-5-of a kind of 7-of preparation oxo-2,3,4, the novel method of 5-tetrahydrochysene-1H-1-benzazepine, its object is to shorten reaction scheme, and two-step reaction one step is completed, improve the quality of products and yield, finally reduce production costs, increase enterprise income.
Technical scheme provided by the invention is as follows:
The chloro-5-oxo-4-carbalkoxy-1-of 7-p-toluenesulfonyl-2,3,4,5-tetrahydrochysene-1-benzazepine, can be by document Chinese Journal of Pharmaceuticals .2009, and 40 (9): the method preparation that 648-650 provides, reaction equation is as follows:
By the chloro-5-oxo-4-carbalkoxy-1-of 7-p-toluenesulfonyl-2,3,4,5-tetrahydrochysene-1-benzazepine is prepared the chloro-5-of 7-oxo-2, during 3,4,5-tetrahydrochysene-1H-1-benzazepine, and " one kettle way " reaction in sulfuric acid.The vitriol oil is joined in there-necked flask; under ice bath, stir 10min; get the chloro-5-oxo-4-carbalkoxy-1-of 7-p-toluenesulfonyl-2,3,4; 5-tetrahydrochysene-1-benzazepine adds in reaction flask; the chloro-5-oxo-4-carbalkoxy-1-of 7-p-toluenesulfonyl-2,3,4; the mol ratio of 5-tetrahydrochysene-1-benzazepine and sulfuric acid is 1: (10-50), and wherein more preferably 1: (35-40).Stir after 15min, reaction system is shifted out to ice bath, reacting by heating, temperature of reaction general control is at 10-100 ℃, fully stirring reaction 30min-5h.After reaction finishes, be cooled to room temperature, in ice bath, with alkali lye, regulate reaction system PH to 7-12, be wherein preferably pH value 7-8.Vacuum filtration, obtains the chloro-5-of deep yellow solid target product 7-oxo-2,3,4,5-tetrahydrochysene-1H-1-benzazepine.Described alkali can be NaOH, KOH, Na
2cO
3or K
2cO
3.
Reaction equation is as follows:
This method compared with prior art, its significant advantage is: shortened the reaction times, the synthetic step of two-step reaction is carried out, simplified reaction scheme, directly adopt the vitriol oil to react, significantly improved speed of reaction, also increased yield, guaranteed quality product, with sulfuric acid replacement hydrochloric acid and PPA, directly reacted simultaneously, not only reduced cost, the sulfuric acid of liquid is also better than thick PPA in reaction.This method also, when having simplified post-treating method, has obtained highly purified product.
Embodiment
Below the specific embodiment of the present invention is described, but be not limited to these embodiment.
The chloro-5-of 7-oxo-2, the preparation of 3,4,5-tetrahydrochysene-1H-1-benzazepine.
embodiment 1
Get 98% the vitriol oil (14.15ml) and be diluted to 85%, join in there-necked flask, under ice bath, stir 10min, get the chloro-5-oxo-4-carbalkoxy-1-of 7-p-toluenesulfonyl-2, 3, 4, 5-tetrahydrochysene-1-benzazepine (2.87g, 0.0065mol) add in reaction flask, stir after 15min, reaction system is shifted out to ice bath, reacting by heating, temperature of reaction system is controlled at 90 ℃, after reaction 1h, TLC detection reaction finishes, stopped reaction, be cooled to room temperature, in ice bath, with NaOH solution (1mol/L), regulate reaction system PH to 7-8, vacuum filtration, obtain the chloro-5-of deep yellow solid target product 7-oxo-2, 3, 4, 5-tetrahydrochysene-1H-1-benzazepine (1.47g, 99%), purity 99% (HPLC, normalization method).
embodiment 2
Get 98% the vitriol oil (14.15ml), join in there-necked flask, under ice bath, stir 10min, get the chloro-5-oxo-4-carbalkoxy-1-of 7-p-toluenesulfonyl-2, 3, 4, 5-tetrahydrochysene-1-benzazepine (2.30g, 0.0052mol) add in reaction flask, stir after 15min, reaction system is shifted out to ice bath, add the 30ml distilled water diluting vitriol oil, under normal temperature, react, after reaction 0.5h, TLC detection reaction finishes, stopped reaction, be cooled to room temperature, in ice bath, with KOH solution (1mol/L), regulate reaction system PH to 9-10, vacuum filtration, obtain the chloro-5-of deep yellow solid target product 7-oxo-2, 3, 4, 5-tetrahydrochysene-1H-1-benzazepine (1.16g, 97%), purity 98.5% (HPLC, normalization method).
embodiment 3
Get 98% the vitriol oil (14.15ml) and be diluted to 50%, join in there-necked flask, under ice bath, stir 10min; get the chloro-5-oxo-4-carbalkoxy-1-of 7-p-toluenesulfonyl-2,3,4; 5-tetrahydrochysene-1-benzazepine (3.28g, 0.0074mol) adds in reaction flask, stirs after 15min; reaction system is shifted out to ice bath, reacting by heating, temperature of reaction system is controlled at 100 ℃; after reaction 5h, TLC detection reaction finishes; stopped reaction, is cooled to room temperature, uses Na in ice bath
2cO
3solution (10mol/L) regulates reaction system PH to 7-8, and vacuum filtration, obtains the chloro-5-of deep yellow solid target product 7-oxo-2,3,4,5-tetrahydrochysene-1H-1-benzazepine (1.66g, 98%), purity 98% (HPLC, normalization method).
embodiment 4
Get 98% the vitriol oil (141.50ml) and be diluted to 65%, join in there-necked flask, under ice bath, stir 10min; get the chloro-5-oxo-4-carbalkoxy-1-of 7-p-toluenesulfonyl-2,3,4; 5-tetrahydrochysene-1-benzazepine (57.38g, 0.13mol) adds in reaction flask, stirs after 15min; reaction system is shifted out to ice bath, reacting by heating, temperature of reaction system is controlled at 80 ℃; after reaction 2h, TLC detection reaction finishes; stopped reaction, is cooled to room temperature, uses K in ice bath
2cO
3solution (10mol/L) regulates reaction system PH to 7～8, and vacuum filtration, obtains the chloro-5-of deep yellow solid target product 7-oxo-2,3,4,5-tetrahydrochysene-1H-1-benzazepine (29.50g, 99%), purity 99% (HPLC, normalization method).
embodiment 5
Get 98% the vitriol oil (141.50ml) and be diluted to 75%, join in there-necked flask, under ice bath, stir 30min, get the chloro-5-oxo-4-carbalkoxy-1-of 7-p-toluenesulfonyl-2, 3, 4, 5-tetrahydrochysene-1-benzazepine (25.50g, 0.0578mol) add in reaction flask, stir after 15min, reaction system is shifted out to ice bath, reacting by heating, temperature of reaction system is controlled at 35 ℃, after reaction 2.5h, TLC detection reaction finishes, stopped reaction, be cooled to room temperature, in ice bath, with NaOH solution (1mol/L), regulate reaction system PH to 11-12, vacuum filtration, obtain the chloro-5-of deep yellow solid target product 7-oxo-2, 3, 4, 5-tetrahydrochysene-1H-1-benzazepine (12.72g, 96%), purity 98.6% (HPLC, normalization method).
embodiment 6
Get 98% the vitriol oil (141.50ml) and be diluted to 80%, join in there-necked flask, under ice bath, stir 35min, get the chloro-5-oxo-4-carbalkoxy-1-of 7-p-toluenesulfonyl-2, 3, 4, 5-tetrahydrochysene-1-benzazepine (38.40g, 0.0867mol) add in reaction flask, stir after 15min, reaction system is shifted out to ice bath, reacting by heating, temperature of reaction system is controlled at 45 ℃, after reaction 3.5h, TLC detection reaction finishes, stopped reaction, be cooled to room temperature, in ice bath, with KOH solution (1mol/L), regulate reaction system PH to 9-10, vacuum filtration, obtain the chloro-5-of deep yellow solid target product 7-oxo-2, 3, 4, 5-tetrahydrochysene-1H-1-benzazepine (19.47g, 98%), purity 99.6% (HPLC, normalization method).
embodiment 7
Get 98% the vitriol oil (28.26ml) and be diluted to 70%, join in there-necked flask, under ice bath, stir 40min, get the chloro-5-oxo-4-carbalkoxy-1-of 7-p-toluenesulfonyl-2, 3, 4, 5-tetrahydrochysene-1-benzazepine (6.56g, 0.0149mol) add in reaction flask, stir after 15min, reaction system is shifted out to ice bath, reacting by heating, temperature of reaction system is controlled at 55 ℃, after reaction 5h, TLC detection reaction finishes, stopped reaction, be cooled to room temperature, in ice bath, with KOH solution (1mol/L), regulate reaction system PH to 9-10, vacuum filtration, obtain the chloro-5-of deep yellow solid target product 7-oxo-2, 3, 4, 5-tetrahydrochysene-1H-1-benzazepine (3.24g, 95%), purity 98.5% (HPLC, normalization method).
embodiment 8
Get 98% the vitriol oil (28.26ml) and be diluted to 90%, join in there-necked flask, under ice bath, stir 15min, get the chloro-5-oxo-4-carbalkoxy-1-of 7-p-toluenesulfonyl-2, 3, 4, 5-tetrahydrochysene-1-benzazepine (9.18g, 0.0208mol) add in reaction flask, stir after 15min, reaction system is shifted out to ice bath, reacting by heating, temperature of reaction system is controlled at 50 ℃, after reaction 3.5h, TLC detection reaction finishes, stopped reaction, be cooled to room temperature, in ice bath, with NaOH solution (1mol/L), regulate reaction system PH to 7-8, vacuum filtration, obtain the chloro-5-of deep yellow solid target product 7-oxo-2, 3, 4, 5-tetrahydrochysene-1H-1-benzazepine (4.72g, 99%), purity 99.8% (HPLC, normalization method).
embodiment 9
Get 98% the vitriol oil (28.26ml) and be diluted to 60%, join in there-necked flask, under ice bath, stir 30min, get the chloro-5-oxo-4-carbalkoxy-1-of 7-p-toluenesulfonyl-2, 3, 4, 5-tetrahydrochysene-1-benzazepine (5.74g, 0.0130mol) add in reaction flask, stir after 15min, reaction system is shifted out to ice bath, reacting by heating, temperature of reaction system is controlled at 70 ℃, after reaction 3h, TLC detection reaction finishes, stopped reaction, be cooled to room temperature, in ice bath, with NaOH solution (1mol/L), regulate reaction system PH to 11-12, vacuum filtration, obtain the chloro-5-of deep yellow solid target product 7-oxo-2, 3, 4, 5-tetrahydrochysene-1H-1-benzazepine (2.89g, 97%), purity 99.5% (HPLC, normalization method).
Claims (9)
1. the chloro-5-of 7-oxo-2, 3, 4, the preparation method of 5-tetrahydrochysene-1H-1-benzazepine, it is characterized in that: get 98% vitriol oil 14.15ml and be diluted to 85%, join in there-necked flask, under ice bath, stir 10min, get 2.87g, the chloro-5-oxo-4-carbalkoxy-1-of 0.0065mol7-p-toluenesulfonyl-2, 3, 4, 5-tetrahydrochysene-1-benzazepine adds in reaction flask, stir after 15min, reaction system is shifted out to ice bath, reacting by heating, temperature of reaction system is controlled at 90 ℃, after reaction 1h, TLC detection reaction finishes, stopped reaction, be cooled to room temperature, in ice bath, with 1mol/L NaOH solution, regulate reaction system pH to 7-8, vacuum filtration, obtain the chloro-5-of deep yellow solid target product 7-oxo-2, 3, 4, 5-tetrahydrochysene-1H-1-benzazepine 1.47g, yield is 99%, through HPLC normalization method, recording purity is 99%.
2. the chloro-5-of 7-oxo-2, 3, 4, the preparation method of 5-tetrahydrochysene-1H-1-benzazepine, it is characterized in that: get 98% vitriol oil 14.15ml, join in there-necked flask, under ice bath, stir 10min, get 2.30g, the chloro-5-oxo-4-carbalkoxy-1-of 0.0052mol7-p-toluenesulfonyl-2, 3, 4, 5-tetrahydrochysene-1-benzazepine adds in reaction flask, stir after 15min, reaction system is shifted out to ice bath, add the 30ml distilled water diluting vitriol oil, under normal temperature, react, after reaction 0.5h, TLC detection reaction finishes, stopped reaction, be cooled to room temperature, in ice bath, with 1mol/L KOH solution, regulate reaction system pH to 9-10, vacuum filtration, obtain the chloro-5-of deep yellow solid target product 7-oxo-2, 3, 4, 5-tetrahydrochysene-1H-1-benzazepine 1.16g, yield is 97%, through HPLC normalization method, recording purity is 98.5%.
3. the chloro-5-of 7-oxo-2, 3, 4, the preparation method of 5-tetrahydrochysene-1H-1-benzazepine, it is characterized in that: get 98% vitriol oil 14.15ml and be diluted to 50%, join in there-necked flask, under ice bath, stir 10min, get 3.28g, the chloro-5-oxo-4-carbalkoxy-1-of 0.0074mol7-p-toluenesulfonyl-2, 3, 4, 5-tetrahydrochysene-1-benzazepine adds in reaction flask, stir after 15min, reaction system is shifted out to ice bath, reacting by heating, temperature of reaction system is controlled at 100 ℃, after reaction 5h, TLC detection reaction finishes, stopped reaction, be cooled to room temperature, in ice bath, use 10mol/L Na
2cO
3solution regulates reaction system pH to 7-8, and vacuum filtration, obtains the chloro-5-of deep yellow solid target product 7-oxo-2,3,4,5-tetrahydrochysene-1H-1-benzazepine 1.66g, and yield 98%, through HPLC normalization method, recording purity is 98%.
4. the chloro-5-of 7-oxo-2, 3, 4, the preparation method of 5-tetrahydrochysene-1H-1-benzazepine, it is characterized in that: get 98% vitriol oil 141.50ml and be diluted to 65%, join in there-necked flask, under ice bath, stir 10min, get 57.38g, the chloro-5-oxo-4-carbalkoxy-1-of 0.13mol7-p-toluenesulfonyl-2, 3, 4, 5-tetrahydrochysene-1-benzazepine adds in reaction flask, stir after 15min, reaction system is shifted out to ice bath, reacting by heating, temperature of reaction system is controlled at 80 ℃, after reaction 2h, TLC detection reaction finishes, stopped reaction, be cooled to room temperature, in ice bath, use 10mol/L K
2cO
3solution regulates reaction system pH to 7～8, and vacuum filtration, obtains the chloro-5-of deep yellow solid target product 7-oxo-2,3,4,5-tetrahydrochysene-1H-1-benzazepine 29.50g, and yield 99%, through HPLC normalization method, recording purity is 99%.
5. the chloro-5-of 7-oxo-2, 3, 4, the preparation method of 5-tetrahydrochysene-1H-1-benzazepine, it is characterized in that: get 98% vitriol oil 141.50ml and be diluted to 75%, join in there-necked flask, under ice bath, stir 30min, get 25.50g, the chloro-5-oxo-4-carbalkoxy-1-of 0.0578mol7-p-toluenesulfonyl-2, 3, 4, 5-tetrahydrochysene-1-benzazepine adds in reaction flask, stir after 15min, reaction system is shifted out to ice bath, reacting by heating, temperature of reaction system is controlled at 35 ℃, after reaction 2.5h, TLC detection reaction finishes, stopped reaction, be cooled to room temperature, in ice bath, with 1mol/L NaOH solution, regulate reaction system pH to 11-12, vacuum filtration, obtain the chloro-5-of deep yellow solid target product 7-oxo-2, 3, 4, 5-tetrahydrochysene-1H-1-benzazepine 12.72g, yield 96%, through HPLC normalization method, recording purity is 98.6%.
6. the chloro-5-of 7-oxo-2, 3, 4, the preparation method of 5-tetrahydrochysene-1H-1-benzazepine, it is characterized in that: get 98% vitriol oil 141.50ml and be diluted to 80%, join in there-necked flask, under ice bath, stir 35min, get 38.40g, the chloro-5-oxo-4-carbalkoxy-1-of 0.0867mol7-p-toluenesulfonyl-2, 3, 4, 5-tetrahydrochysene-1-benzazepine adds in reaction flask, stir after 15min, reaction system is shifted out to ice bath, reacting by heating, temperature of reaction system is controlled at 45 ℃, after reaction 3.5h, TLC detection reaction finishes, stopped reaction, be cooled to room temperature, in ice bath, with 1mol/L KOH solution, regulate reaction system pH to 9-10, vacuum filtration, obtain the chloro-5-of deep yellow solid target product 7-oxo-2, 3, 4, 5-tetrahydrochysene-1H-1-benzazepine 19.47g, yield 98%, through HPLC normalization method, recording purity is 99.6%.
7. the chloro-5-of 7-oxo-2, 3, 4, the preparation method of 5-tetrahydrochysene-1H-1-benzazepine, it is characterized in that: get 98% vitriol oil 28.26ml and be diluted to 70%, join in there-necked flask, under ice bath, stir 40min, get 6.56g, the chloro-5-oxo-4-carbalkoxy-1-of 0.0149mol7-p-toluenesulfonyl-2, 3, 4, 5-tetrahydrochysene-1-benzazepine adds in reaction flask, stir after 15min, reaction system is shifted out to ice bath, reacting by heating, temperature of reaction system is controlled at 55 ℃, after reaction 5h, TLC detection reaction finishes, stopped reaction, be cooled to room temperature, in ice bath, with 1mol/L KOH solution, regulate reaction system pH to 9-10, vacuum filtration, obtain the chloro-5-of deep yellow solid target product 7-oxo-2, 3, 4, 5-tetrahydrochysene-1H-1-benzazepine 3.24g, yield 95%, through HPLC normalization method, recording purity is 98.5%.
8. the chloro-5-of 7-oxo-2, 3, 4, the preparation method of 5-tetrahydrochysene-1H-1-benzazepine, it is characterized in that: get 98% vitriol oil 28.26ml and be diluted to 90%, join in there-necked flask, under ice bath, stir 15min, get 9.18g, the chloro-5-oxo-4-carbalkoxy-1-of 0.0208mol7-p-toluenesulfonyl-2, 3, 4, 5-tetrahydrochysene-1-benzazepine adds in reaction flask, stir after 15min, reaction system is shifted out to ice bath, reacting by heating, temperature of reaction system is controlled at 50 ℃, after reaction 3.5h, TLC detection reaction finishes, stopped reaction, be cooled to room temperature, in ice bath, with 1mol/L NaOH solution, regulate reaction system pH to 7-8, vacuum filtration, obtain the chloro-5-of deep yellow solid target product 7-oxo-2, 3, 4, 5-tetrahydrochysene-1H-1-benzazepine 4.72g, yield 99%, through HPLC normalization method, recording purity is 99.8%.
9. the chloro-5-of 7-oxo-2, 3, 4, the preparation method of 5-tetrahydrochysene-1H-1-benzazepine, it is characterized in that: get 98% vitriol oil 28.26ml and be diluted to 60%, join in there-necked flask, under ice bath, stir 30min, get 5.74g, the chloro-5-oxo-4-carbalkoxy-1-of 0.0130mol7-p-toluenesulfonyl-2, 3, 4, 5-tetrahydrochysene-1-benzazepine adds in reaction flask, stir after 15min, reaction system is shifted out to ice bath, reacting by heating, temperature of reaction system is controlled at 70 ℃, after reaction 3h, TLC detection reaction finishes, stopped reaction, be cooled to room temperature, in ice bath, with 1mol/L NaOH solution, regulate reaction system pH to 11-12, vacuum filtration, obtain the chloro-5-of deep yellow solid target product 7-oxo-2, 3, 4, 5-tetrahydrochysene-1H-1-benzazepine 2.89g, yield 97%, through HPLC normalization method, recording purity is 99.5%.
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| CN103012266B (en) * | 2012-11-23 | 2014-07-23 | 天津药物研究院 | Preparation method of 7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101273017A (en) * | 2005-09-02 | 2008-09-24 | 大塚制药株式会社 | Method of manufacturing benzoazepin compound or its salt |
| CN102093293A (en) * | 2011-03-02 | 2011-06-15 | 宁波人健药业集团有限公司 | Method for preparing 7-chloro-2,3,4,5-tetrahydro-1H-1-benzazepino-5-ketone |
-
2011
- 2011-10-25 CN CN201110326759.5A patent/CN102329268B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101273017A (en) * | 2005-09-02 | 2008-09-24 | 大塚制药株式会社 | Method of manufacturing benzoazepin compound or its salt |
| CN102093293A (en) * | 2011-03-02 | 2011-06-15 | 宁波人健药业集团有限公司 | Method for preparing 7-chloro-2,3,4,5-tetrahydro-1H-1-benzazepino-5-ketone |
Non-Patent Citations (5)
| Title |
|---|
| 7-氯-5-氧代-2,3,4,5-四氢-1H-1-苯并氮杂卓的合成;杨妙等;《中国医药工业杂志》;20091231;第40卷(第9期);648-650 * |
| Kazumi Kondo,et al.7-Chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoyl-amino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine(OPC-41061): A Potent, Orally Active Nonpeptide Arginine Vasopressin V2 Receptor Antagonist.《Bioorganic & Medicinal Chemistry》.1999,第7卷1743-1754. |
| Kazumi Kondo,et al.7-Chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoyl-amino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine(OPC-41061): A Potent, Orally Active Nonpeptide Arginine Vasopressin V2 Receptor Antagonist.《Bioorganic & * |
| Medicinal Chemistry》.1999,第7卷1743-1754. * |
| 杨妙等.7-氯-5-氧代-2,3,4,5-四氢-1H-1-苯并氮杂卓的合成.《中国医药工业杂志》.2009,第40卷(第9期),648-650. |
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