CN103145615A - Posttreatment method of nemonoxacin chelate - Google Patents
Posttreatment method of nemonoxacin chelate Download PDFInfo
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- CN103145615A CN103145615A CN2013100902595A CN201310090259A CN103145615A CN 103145615 A CN103145615 A CN 103145615A CN 2013100902595 A CN2013100902595 A CN 2013100902595A CN 201310090259 A CN201310090259 A CN 201310090259A CN 103145615 A CN103145615 A CN 103145615A
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- nai
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- nemonoxacin
- chelate
- nuosha star
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Abstract
The invention discloses a posttreatment method of a nemonoxacin chelate. The existing posttreatment process of the nemonoxacin chelate is complex, gradient cooling is required, and the time for preparing the chelate is obviously prolonged; and two different solvents toluene and methyl tertiary butyl ether are added for crystallization, which is not environment-friendly and not economical, and also not advantageous for industrial production. The posttreatment method of the nemonoxacin chelate provided by the invention is characterized in that one-step chelation reaction of nemonoxacin cyclized ester is performed to obtain the nemonoxacin chelate, the reaction liquid obtained after the completion of the chelation reaction is mixed with water, the mixture is stirred for crystallization and filtered, and then the obtained crystals are dried so that the nemonoxacin chelate solid is obtained. The posttreatment method provided by the invention is simple in posttreatment process, free of gradient cooling and obviously shortened in operation time; the used solvent is water and the use of organic solvents such as toluene, methyl tertiary butyl ether and the like is avoided, and the yield is obviously improved; therefore, economical efficiency and environmental protection are achieved; and the obtained solid is high in purity, good in free-running property, easy to store and advantageous for carrying out subsequent reaction.
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 pieces of documents are incorporated herein by reference.The synthetic of various quinolone compounds had report in the literature, and for example United States Patent (USP) 6,329, and 391; United States Patent (USP) 6,803,469; Chinese patent CN101045725B; Chinese patent CN101045695B; The people's such as B.Ledoussal " Non6-Fluoro Substituted QuinoloneAntibacterials:Structure and Activity ", J.Med Chem., the 35th volume, the 198th page to 200 pages (1992); The people's such as V.Cecchetti " Studies on6-Aminoquinolines:Synthesis and Antibacterial Evaluation of6-Amino-8-methylquinolones ", Med Chem., the 39th volume, the 436th page to 445 pages (1996); The people's such as V.Cecchetti " Potent6-Desfluoro-8-methylquinolones as New Lead Compounds in Antibacterial Chemotherapy ", J.Med Chem., the 39th volume, the 4952nd page to 4957 pages (1996).
Chinese patent CN101045725B discloses the preparation method of the inner complex intermediate shown in the formula (ⅰ) of Nai Nuosha star in synthetic, the main purpose for preparing this inner complex is, strengthens in follow-up condensation reaction 7-position F as the activity of nucleophilic substitution reaction leavings group.
Formula (ⅰ)
Described method prepares the Nai Nuosha star inner complex shown in formula (ⅰ) take the free acid shown in formula (ⅱ) as starting raw material through chelatropic reaction, and synthetic route is as follows:
Formula (ⅱ) formula (ⅰ)
Yet 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, namely first be cooled to 90 ℃, further be cooled to 50 ℃, be cooled at last 20 ℃, the time of preparation inner complex obviously extends; And add toluene, two kinds of Different solution crystallizations of methyl tertiary butyl ether, neither environmental protection, also uneconomical, be unfavorable for suitability for industrialized production.
Summary of the invention
Technical problem to be solved by this invention is to overcome the defective that above-mentioned existing last handling process exists, a kind of post-treating method of the Nai Nuosha star inner complex that only mixes with the reaction solution that chelatropic reaction obtains take water as solvent is provided, to avoid the use of the organic solvents 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, make 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)
2Be H, alkyl, aryl or heteroaryl;
The reaction solution that obtains after chelatropic reaction is complete mixes with water, and stirring and crystallizing is filtered, and oven dry obtains the Nai Nuosha star inner complex solid shown in formula (ⅳ).
Further, the temperature of described water is preferably 0～30 ℃, is more preferred from 0～10 ℃; The consumption of described water is preferably 5-40 times of the weight of Nai Nuosha star cyclized ester shown in formula (ⅲ), and better is 10～40 times, and the best is 25～30 times; Described hybrid mode is added in reaction solution for reaction solution is added in water or with water.
In above-mentioned chelatropic reaction, the R of carboxylic acid anhydride
2What group was better is alkyl, and that better is C
1～C
4Alkyl, best is methyl; The consumption of carboxylic acid anhydride is better be the molar weight of Nai Nuosha star cyclized ester shown in formula (ⅲ) 3-20 doubly, better is 4.0～10.0 times, best is 5.0～8.0 times; The R of described carboxylic acid
2What group was better is alkyl, 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 better is 1～4 times of 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 better is 0.5～2.0 times of 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; What the temperature that the mixed solvent reaction of boric acid or boric anhydride and carboxylic acid anhydride or carboxylic acid anhydride and carboxylic acid is adopted was better is 90～130 ℃, and better is 110～120 ℃; That the reaction times is better is 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
1What group was better is alkyl, and better is the alkyl of C1～C4, and the best is ethyl; What described temperature of reaction was better is 70～130 ℃, and better is 75～105 ℃, and best is 80～90 ℃; That the reaction times of formula (ⅲ) compound and formula (ⅳ) compound is better is 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, need not gradient cooling, and the operating time obviously shortens; Solvent for use is water, has avoided the use of the organic solvents such as toluene, methyl tertiary butyl ether, and has been 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)
Add aceticanhydride 45ml(476mmol in the 250ml there-necked flask), acetic acid 21.6ml(378mmol) be warming up to 125～130 ℃, add boric anhydride 2.94g(42.2mmol), insulated and stirred 2.5h.Be incubated complete after, reaction solution is cooled to 80～90 ℃, adds the carboxylic acid intermediate 18.1g(65.3mmol shown in formula (ⅱ)), insulated and stirred 6.0h, HPLC monitors reaction result.After reacting completely, reaction solution is added in 0～10 ℃ of frozen water, stirring and crystallizing is filtered, washing, and 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 formulas (ⅲ)
1Base is ethyl) the Nai Nuosha star inner complex shown in preparation formula (ⅰ)
Add aceticanhydride 40ml(423mmol in the 100ml there-necked flask), be warming up to 110～115 ℃, add boric acid 7.2g(116.5mmol), insulated and stirred 1.5h.Be incubated complete after, reaction solution is cooled to 80～90 ℃, adds the Nai Nuosha star cyclized ester 22.5g(73.7mmol shown in formula (ⅲ)), insulated and stirred 3.5h, HPLC monitors reaction result.After reacting completely, reaction solution is added in 0～10 ℃ of frozen water, stirring and crystallizing is filtered, washing, and 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 formulas (ⅲ)
1Base is H) the Nai Nuosha star inner complex shown in preparation formula (ⅰ)
Add aceticanhydride 45ml(476mmol in the 250ml there-necked flask), acetic acid 21.6ml(378mmol) be warming up to 125～130 ℃, add boric anhydride 2.94g(42.2mmol), insulated and stirred 2.5h.Be incubated complete after, reaction solution is cooled to 80～90 ℃, adds the carboxylic acid intermediate 18.1g(65.3mmol shown in formula (ⅱ)), insulated and stirred 6.0h, HPLC monitors reaction result.After reacting completely, close heating, 0～10 ℃ of frozen water is added in reaction solution, stirring and crystallizing is filtered, washing, and 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 Examples CN101045725 embodiment 1 formula (ⅱ)
With boron oxide (2.0kg, the 29mol) reactor of packing into, use subsequently the dilution of Glacial acetic acid (8.1L, 142mol) and diacetyl oxide (16.2L, 171mol).With the gained mixture heating up to reflux temperature at least 2 hours.Reactant is cooled to 40 ℃, 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.Carry out with HPLC and NMR monitoring reaction.Mixture is cooled to approximately 90 ℃, and toluene (45L) is added in reaction.To react and further be cooled to 50 ℃, and tert-butyl methyl ether (19L) will be added in reaction mixture to impel the product precipitation.Then mixture is cooled to 20 ℃, and by filtering to isolate the inner complex shown in solid type (ⅰ).Then wash isolated solid with tert-butyl methyl ether (26L) before drying in 40 ℃ of vacuum ovens (50 holder).The product yield that obtains at the Nai Nuosha star inner complex shown in this reaction Chinese style (ⅰ) is 86.4%.
By Comparative Examples as can be known, the post-treating method of the Nai Nuosha star inner complex shown in original preparation formula (ⅰ) is compared the present invention's length consuming time, complicated operation, and organic solvent used is many, and neither environmental protection is uneconomical again, and yield is on the low side, is unfavorable for suitability for industrialized production.
Claims (7)
1. the post-treating method of Yi Zhong Nai Nuosha star inner complex, make 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, and 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)
2Be H, alkyl, aryl or heteroaryl;
The reaction solution that obtains after chelatropic reaction is complete mixes with water, and stirring and crystallizing is filtered, and oven dry obtains the Nai Nuosha star inner complex solid shown in formula (ⅳ).
2. the post-treating method of Nai Nuosha star inner complex according to claim 1, it is characterized in that: the temperature of described water is 0～30 ℃.
3. the post-treating method of Nai Nuosha star inner complex according to claim 2, it is characterized in that: the temperature of described water is 0～10 ℃.
4. the post-treating method of Nai Nuosha star inner complex according to claim 1 is characterized in that: the consumption of described water be the weight of Nai Nuosha star cyclized ester shown in formula (ⅲ) 5-40 doubly.
5. the post-treating method of Nai Nuosha star inner complex according to claim 4 is characterized in that: the consumption of described water is 10～40 times of weight of Nai Nuosha star cyclized ester shown in formula (ⅲ).
6. the post-treating method of Nai Nuosha star inner complex according to claim 5 is characterized in that: the consumption of described water is 25～30 times of weight of Nai Nuosha star cyclized ester shown in formula (ⅲ).
7. the post-treating method of Nai Nuosha star inner complex according to claim 1, it is characterized in that: described hybrid mode is added in reaction solution for reaction solution is added in water or with water.
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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 |
|---|
| 刘九雨,等: "莫西沙星8-二氟甲氧基类似物的合成与体内外抗菌作用", 《中国抗生素杂志》, vol. 31, no. 09, 30 September 2006 (2006-09-30), pages 539 - 562 * |
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