CN103145615B - A kind of post-treating method of Nai Nuosha star inner complex - Google Patents
A kind of post-treating method of Nai Nuosha star inner complex Download PDFInfo
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Abstract
The invention discloses a kind of post-treating method of Nai Nuosha star inner complex.The last handling process of existing Nai Nuosha star inner complex is complicated, and need gradient cooling, the time of preparing inner complex obviously extends; And add toluene, methyl tertiary butyl ether two kinds of Different solution crystallizations, both not environmentally, also uneconomical, be unfavorable for suitability for industrialized production.The invention is characterized in and obtain Nai Nuosha star inner complex by Nai Nuosha star cyclized ester through a step chelatropic reaction, the reaction solution obtained after chelatropic reaction is complete mixes with water, and stirring and crystallizing is filtered, and dries and obtains Nai Nuosha star inner complex solid.Last handling process of the present invention is simple, and without the need to gradient cooling, the operating time obviously shortens; Solvent for use is water, avoids the use of the organic solvent such as toluene, methyl tertiary butyl ether, and is significantly improved on yield, not only economy but also environmental protection; Gained solid purity is high, and free-running property is good, is easy to store, and is conducive to the carrying out of subsequent reactions.
Description
Technical field
The present invention relates to the aftertreatment of Nai Nuosha star intermediate, specifically a kind of post-treating method of Nai Nuosha star inner complex.
Background technology
Antimicrobial quinolone compounds Nai Nuosha star (3S, 5S)-7-[3-amino-5-methyl-piperidyl]-1-cyclopropyl-1,4-dihydro-8-methoxyl group-4-oxo-3-quinoline carboxylic acid is disclosed in United States Patent (USP) 6,329,391, its malate and polymorphic form are disclosed in Chinese patent CN101045725B, and these two sections of references cited therein are for reference.The synthesis of various quinolone compounds has report in the literature, such as United States Patent (USP) 6, and 329,391; United States Patent (USP) 6,803,469; Chinese patent CN101045725B; Chinese patent CN101045695B; " the Non6-Fluoro Substituted QuinoloneAntibacterials:Structure and Activity " of the people such as B.Ledoussal, J.Med Chem., the 35th volume, the 198th page to 200 pages (1992); " the Studies on6-Aminoquinolines:Synthesis and Antibacterial Evaluation of6-Amino-8-methylquinolones " of the people such as V.Cecchetti, Med Chem., 39th volume, the 436th page to 445 pages (1996); " the Potent6-Desfluoro-8-methylquinolones as New Lead Compounds in Antibacterial Chemotherapy " of the people such as V.Cecchetti, J.Med Chem., 39th volume, the 4952nd page to 4957 pages (1996).
Chinese patent CN101045725B discloses the preparation method of the inner complex intermediate shown in formula (I) in the synthesis of Nai Nuosha star, the main purpose preparing this inner complex is, to strengthen in follow-up condensation reaction 7-position F as the activity of nucleophilic substitution reaction leavings group.
Formula (I)
Described method is with the free acid shown in formula (II) for starting raw material, and prepare the Nai Nuosha star inner complex shown in formula (I) through chelatropic reaction, synthetic route is as follows:
Formula (II) formula (I)
But in the method for the Nai Nuosha star inner complex shown in above-mentioned preparation formula (I), the last handling process of Nai Nuosha star inner complex is complicated, need gradient cooling, be namely first cooled to 90 DEG C, be cooled to 50 DEG C further, finally be cooled to 20 DEG C, the time of preparing inner complex obviously extends; And add toluene, methyl tertiary butyl ether two kinds of Different solution crystallizations, both not environmentally, also uneconomical, be unfavorable for suitability for industrialized production.
Summary of the invention
Technical problem to be solved by this invention is the defect overcoming above-mentioned existing last handling process existence, thering is provided a kind of is only the post-treating method of the Nai Nuosha star inner complex that solvent mixes with the reaction solution that chelatropic reaction obtains with water, to avoid the use of the organic solvent such as toluene, methyl tertiary butyl ether, simplify last handling process, shorten the operating time.
For this reason, the present invention adopts following technical scheme: a kind of post-treating method of Nai Nuosha star inner complex, obtain the Nai Nuosha star inner complex shown in formula (IV) by the Nai Nuosha star cyclized ester shown in formula (III) through a step chelatropic reaction, the synthetic route of aforesaid method is as follows:
Wherein, the R shown in formula (III)
1be selected from alkyl, aryl or heteroaryl; R shown in formula (IV)
2for H, alkyl, aryl or heteroaryl;
The reaction solution obtained after chelatropic reaction is complete mixes with water, and stirring and crystallizing is filtered, and dries and obtains the Nai Nuosha star inner complex solid shown in formula (IV).
Further, the temperature of described water is preferably 0 ~ 30 DEG C, is more preferred from 0 ~ 10 DEG C; The consumption of described water is preferably the 5-40 of the weight of Nai Nuosha star cyclized ester shown in formula (III) doubly, and better is 10 ~ 40 times, and the best is 25 ~ 30 times; Described hybrid mode is added in reaction solution for being added in water or by water by reaction solution.
In above-mentioned chelatropic reaction, the R of carboxylic acid anhydride
2group is alkyl than preferably, and that better is C
1~ C
4alkyl, best is methyl; The consumption of carboxylic acid anhydride is preferably 3-20 times of the molar weight of Nai Nuosha star cyclized ester shown in formula (III), and better is 4.0 ~ 10.0 times, and best is 5.0 ~ 8.0 times; The R of described carboxylic acid
2group is alkyl than preferably, and that better is C
1~ C
4alkyl, best is methyl; Shown in carboxylic acid and formula (III), the molar ratio of Nai Nuosha star cyclized ester is 1-20:1; The consumption of described boric acid is preferably 1 ~ 4 times of the molar weight of Nai Nuosha star cyclized ester shown in formula (III), and better is 1.0 ~ 2.5 times, and best is 1.2 ~ 1.6 times; The consumption of described boric anhydride is preferably 0.5 ~ 2.0 times of the molar weight of Nai Nuosha star cyclized ester shown in formula (III), and better is 0.5 ~ 1.0 times, and best is 0.6 ~ 0.8 times; The mixed solvent of boric acid or boric anhydride and carboxylic acid anhydride or carboxylic acid anhydride and carboxylic acid reacts the temperature adopted and is preferably 90 ~ 130 DEG C, and better is 110 ~ 120 DEG C; Reaction times is preferably 0.5 ~ 5.0h, and that better is 1.0 ~ 3.0h.
In above-mentioned chelatropic reaction, the R of described Nai Nuosha star cyclized ester
1group is preferably alkyl, the alkyl of better is C1 ~ C4, and the best is ethyl; Described temperature of reaction is preferably 70 ~ 130 DEG C, and better is 75 ~ 105 DEG C, and best is 80 ~ 90 DEG C; The reaction times of formula (III) compound and formula (IV) compound is preferably 0.5 ~ 15.0h, and that better is 2.0 ~ 6.0h, and that best is 3.0 ~ 5.0h.
Last handling process of the present invention is simple, and without the need to gradient cooling, the operating time obviously shortens; Solvent for use is water, avoids the use of the organic solvent such as toluene, methyl tertiary butyl ether, and is significantly improved on yield, not only economy but also environmental protection; Gained solid purity is high, and free-running property is good, is easy to store, and is conducive to the carrying out of subsequent reactions.
Embodiment:
Mode below by embodiment further illustrates the present invention, but does not therefore limit the present invention among described scope of embodiments.
Carboxylic acid intermediate (R shown in embodiment 1 formula (III)
1base is H) the Nai Nuosha star inner complex shown in preparation formula (I)
Aceticanhydride 45ml(476mmol is added in 250ml there-necked flask), acetic acid 21.6ml(378mmol) be warming up to 125 ~ 130 DEG C, add boric anhydride 2.94g(42.2mmol), insulated and stirred 2.5h.After insulation, reaction solution is cooled to 80 ~ 90 DEG C, adds the carboxylic acid intermediate 18.1g(65.3mmol shown in formula (II)), insulated and stirred 6.0h, HPLC monitor reaction result.After reacting completely, be added to by reaction solution in 0 ~ 10 DEG C of frozen water, stirring and crystallizing, filter, washing, vacuum-drying obtains off-white color solid 24.5g, HPLC purity 99.5%, yield 92.7%.
NMR(CDCl
3，400MHz)δ(ppm)：9.23(s，1H)，8.37-8.33(m，1H)，7.55(t，J＝9.8Hz，1H)，4.43-4.40(m，1H)，4.14(s，3H)，2.04(s，6H)，1.45-1.42(m，2H)，1.33-1.30(m，2H)。
Intermediate (R shown in embodiment 2 formula (III)
1base is ethyl) the Nai Nuosha star inner complex shown in preparation formula (I)
Aceticanhydride 40ml(423mmol is added in 100ml there-necked flask), be warming up to 110 ~ 115 DEG C, add boric acid 7.2g(116.5mmol), insulated and stirred 1.5h.After insulation, reaction solution is cooled to 80 ~ 90 DEG C, adds the Nai Nuosha star cyclized ester 22.5g(73.7mmol shown in formula (III)), insulated and stirred 3.5h, HPLC monitor reaction result.After reacting completely, be added to by reaction solution in 0 ~ 10 DEG C of frozen water, stirring and crystallizing, filter, washing, vacuum-drying obtains off-white color solid 28.4g, HPLC purity 99.2%, yield 95.1%.
NMR(CDCl
3，400MHz)δ(ppm)：9.23(s，1H)，8.37-8.33(m，1H)，7.55(t，J＝9.8Hz，1H)，4.43-4.40(m，1H)，4.14(s，3H)，2.04(s，6H)，1.45-1.42(m，2H)，1.33-1.30(m，2H)。
Carboxylic acid intermediate (R shown in embodiment 3 formula (III)
1base is H) the Nai Nuosha star inner complex shown in preparation formula (I)
Aceticanhydride 45ml(476mmol is added in 250ml there-necked flask), acetic acid 21.6ml(378mmol) be warming up to 125 ~ 130 DEG C, add boric anhydride 2.94g(42.2mmol), insulated and stirred 2.5h.After insulation, reaction solution is cooled to 80 ~ 90 DEG C, adds the carboxylic acid intermediate 18.1g(65.3mmol shown in formula (II)), insulated and stirred 6.0h, HPLC monitor reaction result.After reacting completely, close heating, be added in reaction solution, stirring and crystallizing by 0 ~ 10 DEG C of frozen water, filter, washing, vacuum-drying obtains off-white color solid 24.3g, HPLC purity 99.0%, yield 92.0%.
NMR(CDCl
3，400MHz)δ(ppm)：9.23(s，1H)，8.37-8.33(m，1H)，7.55(t，J＝9.8Hz，1H)，4.43-4.40(m，1H)，4.14(s，3H)，2.04(s，6H)，1.45-1.42(m，2H)，1.33-1.30(m，2H)。
Nai Nuosha star inner complex shown in carboxylic acid intermediate preparation formula (I) shown in comparative example CN101045725 embodiment 1 formula (II)
Boron oxide (2.0kg, 29mol) is loaded reactor, uses Glacial acetic acid (8.1L, 142mol) and diacetyl oxide (16.2L, 171mol) dilution subsequently.Gained mixture is heated to reflux temperature at least 2 hours.Reactant is cooled to 40 DEG C, and the carboxylic acid intermediate (14.2kg, 51mol) shown in formula (II) is added to reaction mixture.Mixture is heated to reflux temperature at least 6 hours again.Monitor reaction with HPLC and NMR to carry out.Mixture is cooled to about 90 DEG C, and toluene (45L) is added in reaction.Reaction is cooled to 50 DEG C further, and tert-butyl methyl ether (19L) is added in reaction mixture to impel product to precipitate.Then mixture is cooled to 20 DEG C, and by filtering to isolate the inner complex shown in solid type (I).Then in 40 DEG C of vacuum ovens (50 holder), isolated solid is washed with tert-butyl methyl ether (26L) before drying.The product yield that Nai Nuosha star inner complex in the reaction shown in formula (I) obtains is 86.4%.
From comparative example, the post-treating method of the Nai Nuosha star inner complex shown in original preparation formula (I) compares the present invention's length consuming time, complicated operation, and organic solvent used is many, and not only not environmentally but also uneconomical, and yield is on the low side, is unfavorable for suitability for industrialized production.
Claims (2)
1. the post-treating method of Yi Zhong Nai Nuosha star inner complex, obtain the Nai Nuosha star inner complex shown in formula (IV) by the Nai Nuosha star cyclized ester shown in formula (III) through a step chelatropic reaction, the synthetic route of aforesaid method is as follows:
Wherein, the R shown in formula (III)
1for C
1-4alkyl; R shown in formula (IV)
2for H or C
1-4alkyl;
The reaction solution obtained after chelatropic reaction is complete mixes with water, without the need to gradient cooling, stirring and crystallizing, filter, oven dry obtains the Nai Nuosha star inner complex solid shown in formula (IV), the temperature of described water is 0 ~ 10 DEG C, and the consumption of described water is 25 ~ 30 times of the weight of Nai Nuosha star cyclized ester shown in formula (III), and the temperature of reaction of chelating is 80 ~ 90 DEG C.
2. the post-treating method of Nai Nuosha star inner complex according to claim 1, is characterized in that: described hybrid mode is added in reaction solution for being added in water or by water by reaction solution.
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Citations (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1630655A (en) * | 2001-10-04 | 2005-06-22 | 莫弗凯姆联合化学股份公司 | Dual action antibiotics |
| CN1660838A (en) * | 2004-12-30 | 2005-08-31 | 南京圣和药业有限公司 | Method for preparing and purifying laevogyrate gatifloxacin |
| CN101045695A (en) * | 2006-03-28 | 2007-10-03 | 宝洁公司 | Hydro-reduction method for preparing quinolone intermediate |
| CN101045724A (en) * | 2006-03-28 | 2007-10-03 | 宝洁公司 | Coupling method for preparing quinolone intermediate |
| WO2007110836A1 (en) * | 2006-03-28 | 2007-10-04 | The Procter & Gamble Company | A hydride reduction process for preparing quinolone intermediates |
| WO2007110834A2 (en) * | 2006-03-28 | 2007-10-04 | The Procter & Gamble Company | Malate salts, and polymorphs of (3s,5s)-7-[3-amino-5-methyl-piperidinyl]-1-cyclopropyl-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid |
| WO2007110835A2 (en) * | 2006-03-28 | 2007-10-04 | The Procter & Gamble Company | A coupling process for preparing quinolone intermediates |
| WO2009023473A2 (en) * | 2007-08-09 | 2009-02-19 | Taigen Biotechnology Co., Ltd. | Antimicrobial parenteral formulation |
| US20090156577A1 (en) * | 2004-09-09 | 2009-06-18 | Benjamin Davis | 7-amino alkylidenyl-heterocyclic quinolones and naphthyridones |
| CN101618038A (en) * | 2008-07-01 | 2010-01-06 | 太景生物科技股份有限公司 | Treatment of antibiotic-resistant bacteria infection |
| CN101628911A (en) * | 2008-07-15 | 2010-01-20 | 太景生物科技股份有限公司 | Antibiotic drug |
| CN101973992A (en) * | 2010-10-09 | 2011-02-16 | 河南省健康伟业医药科技有限公司 | Synthesizing method of moxifloxacin hydrochloride |
| CN102351858A (en) * | 2011-09-21 | 2012-02-15 | 浙江新东港药业股份有限公司 | High selectivity method for synthesizing moxifloxacin |
| CN102558183A (en) * | 2010-12-08 | 2012-07-11 | 南京明生医药技术有限公司 | Pyrrolidine pyrazolyl oxo-quinoline carboxylic acid compound |
-
2013
- 2013-03-20 CN CN201310090259.5A patent/CN103145615B/en active Active
Patent Citations (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1630655A (en) * | 2001-10-04 | 2005-06-22 | 莫弗凯姆联合化学股份公司 | Dual action antibiotics |
| US20090156577A1 (en) * | 2004-09-09 | 2009-06-18 | Benjamin Davis | 7-amino alkylidenyl-heterocyclic quinolones and naphthyridones |
| CN1660838A (en) * | 2004-12-30 | 2005-08-31 | 南京圣和药业有限公司 | Method for preparing and purifying laevogyrate gatifloxacin |
| WO2007110835A2 (en) * | 2006-03-28 | 2007-10-04 | The Procter & Gamble Company | A coupling process for preparing quinolone intermediates |
| WO2007110836A1 (en) * | 2006-03-28 | 2007-10-04 | The Procter & Gamble Company | A hydride reduction process for preparing quinolone intermediates |
| WO2007110834A2 (en) * | 2006-03-28 | 2007-10-04 | The Procter & Gamble Company | Malate salts, and polymorphs of (3s,5s)-7-[3-amino-5-methyl-piperidinyl]-1-cyclopropyl-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid |
| CN101045724A (en) * | 2006-03-28 | 2007-10-03 | 宝洁公司 | Coupling method for preparing quinolone intermediate |
| CN101045695A (en) * | 2006-03-28 | 2007-10-03 | 宝洁公司 | Hydro-reduction method for preparing quinolone intermediate |
| WO2009023473A2 (en) * | 2007-08-09 | 2009-02-19 | Taigen Biotechnology Co., Ltd. | Antimicrobial parenteral formulation |
| CN101618038A (en) * | 2008-07-01 | 2010-01-06 | 太景生物科技股份有限公司 | Treatment of antibiotic-resistant bacteria infection |
| CN101628911A (en) * | 2008-07-15 | 2010-01-20 | 太景生物科技股份有限公司 | Antibiotic drug |
| CN101973992A (en) * | 2010-10-09 | 2011-02-16 | 河南省健康伟业医药科技有限公司 | Synthesizing method of moxifloxacin hydrochloride |
| CN102558183A (en) * | 2010-12-08 | 2012-07-11 | 南京明生医药技术有限公司 | Pyrrolidine pyrazolyl oxo-quinoline carboxylic acid compound |
| CN102351858A (en) * | 2011-09-21 | 2012-02-15 | 浙江新东港药业股份有限公司 | High selectivity method for synthesizing moxifloxacin |
Non-Patent Citations (1)
| Title |
|---|
| 莫西沙星8-二氟甲氧基类似物的合成与体内外抗菌作用;刘九雨,等;《中国抗生素杂志》;20060930;第31卷(第09期);第539-562页 * |
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