CN101787021A - High-purified tropisetron hydrochloride compound - Google Patents
High-purified tropisetron hydrochloride compound Download PDFInfo
- Publication number
- CN101787021A CN101787021A CN 201010117917 CN201010117917A CN101787021A CN 101787021 A CN101787021 A CN 101787021A CN 201010117917 CN201010117917 CN 201010117917 CN 201010117917 A CN201010117917 A CN 201010117917A CN 101787021 A CN101787021 A CN 101787021A
- Authority
- CN
- China
- Prior art keywords
- tropisetron
- obtains
- volume
- moving phase
- tropisetron hydrochloride
- 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.)
- Granted
Links
- 229960003674 tropisetron hydrochloride Drugs 0.000 title claims abstract description 30
- -1 tropisetron hydrochloride compound Chemical class 0.000 title claims abstract description 14
- 238000000746 purification Methods 0.000 claims abstract description 15
- 238000000926 separation method Methods 0.000 claims abstract description 8
- ZNRGQMMCGHDTEI-ITGUQSILSA-N tropisetron Chemical compound C1=CC=C2C(C(=O)O[C@H]3C[C@H]4CC[C@@H](C3)N4C)=CNC2=C1 ZNRGQMMCGHDTEI-ITGUQSILSA-N 0.000 claims description 41
- 229960003688 tropisetron Drugs 0.000 claims description 25
- 239000000706 filtrate Substances 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 14
- 238000001035 drying Methods 0.000 claims description 14
- 238000003756 stirring Methods 0.000 claims description 14
- 239000000047 product Substances 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 10
- 238000004237 preparative chromatography Methods 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- RNTXMYSPASRLFT-UHFFFAOYSA-L disodium;2-[[n'-[hydroxy(oxido)phosphoryl]carbamimidoyl]-methylamino]acetate Chemical compound [Na+].[Na+].OC(=O)CN(C)C(N)=NP([O-])([O-])=O RNTXMYSPASRLFT-UHFFFAOYSA-L 0.000 claims description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 7
- 239000012043 crude product Substances 0.000 claims description 7
- 238000005261 decarburization Methods 0.000 claims description 7
- 238000001556 precipitation Methods 0.000 claims description 7
- 239000000741 silica gel Substances 0.000 claims description 7
- 229910002027 silica gel Inorganic materials 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 235000017550 sodium carbonate Nutrition 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical group CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 3
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 14
- 238000010669 acid-base reaction Methods 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 2
- 229940079593 drug Drugs 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 238000001179 sorption measurement Methods 0.000 abstract 1
- XIEGSJAEZIGKSA-LUNMCBQDSA-N tropisetron hydrochloride Chemical compound Cl.C1=CC=C2C(C(=O)O[C@H]3C[C@H]4CC[C@@H](C3)N4C)=CNC2=C1 XIEGSJAEZIGKSA-LUNMCBQDSA-N 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 229910052739 hydrogen Inorganic materials 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 206010047700 Vomiting Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000000578 peripheral nerve Anatomy 0.000 description 2
- 238000007670 refining Methods 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- KMAKOBLIOCQGJP-UHFFFAOYSA-N indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CNC2=C1 KMAKOBLIOCQGJP-UHFFFAOYSA-N 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000013094 purity test Methods 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a tropisetron hydrochloride compound. The purity of the tropisetron hydrochloride is greatly improved by acid-base reaction, activated carbon adsorption and separation and purification prepared chromatographic columns, thus optimizing the quality of preparation products and the safety of clinical medication. The method has simple process, low cost and high yield, and is applicable to industrial production.
Description
Technical field
The present invention relates to a kind of Tropisetron hydrochloride compound, can obtain highly purified Tropisetron hydrochloride, belong to medical technical field by method of the present invention.
Background technology
Tropisetron hydrochloride, its chemical name is: interior-the 1H-Indole-3-Carboxylic Acid-the 8-methyl-8-azabicyclo [3.2.1] oct-3-yl ester hydrochloride, molecular formula: C
17H
20N
2O
2HCl, molecular weight: 320.81, structural formula is:
Tropisetron hydrochloride is that a kind of peripheral nerve potent, highly selective former and central nervous system serotonin 3 (5-HT3) acceptor are competed antagonist, mainly suppresses vomiting reflex by optionally blocking the former presynaptic 5-HT3 of peripheral nerve acceptor.Be applicable to the nausea and vomiting that prevention and treatment cancer chemotherapy cause.
The synthetic method bibliographical information of Tropisetron hydrochloride is more, is exactly that the finished product purity that obtains is lower but there is a common defective, has influenced the security of pharmaceutical preparation.
Summary of the invention
The object of the present invention is to provide a kind of process for purification of Tropisetron hydrochloride compound, pass through acidification reaction, charcoal absorption and preparative chromatography column separating purification reach the purpose of refining purifying, finally obtain highly purified Tropisetron hydrochloride compound, optimize quality product, ensured safety of clinical administration.
The process for purification of Tropisetron hydrochloride compound provided by the invention comprises the steps:
(1) the Tropisetron hydrochloride crude product is soluble in water, slowly add alkali then, stirring reaction to pH value of solution is 7-10, generation tropisetron precipitation is filtered 35-50 ℃ of drying under reduced pressure, obtain tropisetron, described alkali is sodium hydroxide, potassium hydroxide, yellow soda ash or sodium bicarbonate;
(2) will go up the tropisetron that obtains of step is dissolved in the solvent of 2-10 times of weight, the gac that adds overall solution volume 0.01-0.05 (g/ml), 20-50 ℃ was stirred 0.5-1.5 hour, filtered decarburization, collect filtrate, wherein said solvent is selected from propyl carbinol, normal hexane or ethanol;
(3) will go up the filtrate that obtains of step and utilize the preparative chromatography post to carry out separation and purification to obtain the Disodium phosphocreatine highly finished product, wherein the moving phase used of chromatographic column accounts for the methylene dichloride of moving phase 30-50% or acetone and volume as volume and accounts for the aqueous hydrochloric acid of the pH of moving phase 50-70% as 1-2; Fixed phase stuffing is selected from silica gel or aluminum oxide; Flow velocity is 4.5-6.8ml/min; Column temperature: 20-25 ℃.Collect filtrate, drying under reduced pressure obtains the purified Tropisetron hydrochloride.
As a preferred embodiment of the present invention, wherein the middle stirring reaction of step (1) is to pH value of solution value 7-9.
As a preferred embodiment of the present invention, the preferred sodium hydroxide of alkali in the step (1) wherein.
As a preferred embodiment of the present invention, wherein add the gac of overall solution volume 0.02-0.03 (g/ml) in the step (2), whip attachment 30-50 minute.
The process for purification of Tropisetron hydrochloride compound provided by the invention, by acid-base reaction, charcoal absorption and preparative chromatography column separating purification have improved the purity of Tropisetron hydrochloride greatly, have optimized the quality product of preparation, have ensured safety of clinical administration; Present method technology is simple, and cost is low, and the yield height is suitable for suitability for industrialized production.
Embodiment
Below further explain and describe content of the present invention by embodiment, but embodiment is not to be construed as limiting the scope of the invention.
Purity testing is undertaken by high performance liquid chromatography with reference to two appendix VD of Chinese Pharmacopoeia version in 2005.The filling of the preparative chromatography post that uses in the treating process is undertaken by ordinary method.Determine that by nucleus magnetic resonance and infrared spectra the resulting product in refining back is a Disodium phosphocreatine.
Making with extra care of embodiment 1 Tropisetron hydrochloride
(1) 50g Tropisetron hydrochloride crude product is dissolved in the 500ml water, slowly adds the sodium carbonate solution of 10% (g/ml) then, stirring reaction to pH value of solution is 8, produces the tropisetron precipitation, filters, and 50 ℃ of drying under reduced pressure obtain tropisetron 41.7g.
(2) will go up the tropisetron 41.7g that obtains of step and be dissolved in the 300ml propyl carbinol, and add the gac of 3.5g, stirring at room 35 minutes is filtered decarburization, collects filtrate.
(3) will go up the filtrate that obtains of step and utilize the preparative chromatography post to carry out separation and purification to obtain the Disodium phosphocreatine highly finished product, wherein to account for the methylene dichloride of moving phase 35% and pH that volume accounts for moving phase 65% as volume be 1 aqueous hydrochloric acid to the moving phase used of chromatographic column; Fixed phase stuffing is a silica gel; Flow velocity is 4.8ml/min; Column temperature: 22 ℃.Collect filtrate, drying under reduced pressure obtains purified Tropisetron hydrochloride 45.8g, yield 91.6%, and HPLC method purity is 99.9%.
Ultimate analysis: C
17H
21ClN
2O
2
Theoretical value (%): C:63.65, H:6.60, N:8.73, Cl:11.05;
Measured value (%): C:63.55, H:6.62, N:8.75, Cl:11.08.
UV(MeOH)λ
max：214(ε38，222)，229(ε17，438)，282(ε13，405)。
IR(KCl)cm
-1：3219，2496(N-H)，3103，748(Ar?C-H)，2966，1428(C-H)，1692(C＝O)，1580，1525(Ar?C＝C)，1311，1128(C-N)，1033(C-O)。
1HNMR(DMSO-D
6)δ：2.10(d，2H，CH
2)，2.32(d，4H，CH
2)，2.52(m，2H，CH
2)，2.68(s，3H，CH
3)，3.88(s，2H，-CH)，5.14(s，H，CH)，8.03(m，H，CH)，8.08(d，H，CH)，10.81(s，H，HCl)，12.10(s，H，NH)。ESI-MS；EI?m/z：285(M+H，100％)，284(M
+，21.72％)。
Making with extra care of embodiment 2 Tropisetron hydrochlorides
(1) 50g Tropisetron hydrochloride crude product is dissolved in the 500ml water, slowly adds the sodium hydroxide solution of 8% (g/ml) then, stirring reaction to pH value of solution is 9, produces the tropisetron precipitation, filters, and 40 ℃ of drying under reduced pressure obtain tropisetron 41.3g.
(2) will go up the tropisetron 41.3g that obtains of step and be dissolved in the 300ml normal hexane, and add the gac of 3.3g, stirring at room 45 minutes is filtered decarburization, collects filtrate.
(3) will go up the filtrate that obtains of step and utilize the preparative chromatography post to carry out separation and purification to obtain the Disodium phosphocreatine highly finished product, wherein to account for the methylene dichloride of moving phase 45% and pH that volume accounts for moving phase 55% as volume be 1 aqueous hydrochloric acid to the moving phase used of chromatographic column; Fixed phase stuffing is a silica gel; Flow velocity is 5.2ml/min; Column temperature: 20 ℃.Collect filtrate, drying under reduced pressure obtains purified Tropisetron hydrochloride 46.2g, yield 92.4%, and HPLC method purity is 99.8%.
Ultimate analysis: C
17H
21ClN
2O
2
Theoretical value (%): C:63.65, H:6.60, N:8.73, Cl:11.05;
Measured value (%): C:63.58, H:6.61, N:8.70, Cl:11.06.
UV(MeOH)λ
max：214(ε38，222)，229(ε17，438)，282(ε13，405)。
IR(KCl)cm
-1：3219，2496(N-H)，3103，748(Ar?C-H)，2966，1428(C-H)，1692(C＝O)，1580，1525(Ar?C＝C)，1311，1128(C-N)，1033(C-O)。
1HNMR(DMSO-D
6)δ：2.10(d，2H，CH
2)，2.32(d，4H，CH
2)，2.52(m，2H，CH
2)，2.68(s，3H，CH
3)，3.88(s，2H，-CH)，5.14(s，H，CH)，8.03(m，H，CH)，8.08(d，H，CH)，10.81(s，H，HCl)，12.10(s，H，NH)。ESI-MS；EI?m/z：285(M+H，100％)，284(M
+，21.72％)。
Making with extra care of embodiment 3 Tropisetron hydrochlorides
(1) 50g Tropisetron hydrochloride crude product is dissolved in the 500ml water, slowly adds the sodium hydrogen carbonate solution of 12% (g/ml) then, stirring reaction to pH value of solution is 7, produces the tropisetron precipitation, filters, and 40 ℃ of drying under reduced pressure obtain tropisetron 42.0g.
(2) will go up the tropisetron 42.0g that obtains of step and be dissolved in the 300ml normal hexane, and add the gac of 3.2g, stirring at room 40 minutes is filtered decarburization, collects filtrate.
(3) will go up the filtrate that obtains of step and utilize the preparative chromatography post to carry out separation and purification to obtain the Disodium phosphocreatine highly finished product, wherein to account for the methylene dichloride of moving phase 40% and pH that volume accounts for moving phase 60% as volume be 1 aqueous hydrochloric acid to the moving phase used of chromatographic column; Fixed phase stuffing is a silica gel; Flow velocity is 5.4ml/min; Column temperature: 25 ℃.Collect filtrate, drying under reduced pressure obtains purified Tropisetron hydrochloride 45.4g, yield 90.8%, and HPLC method purity is 99.7%.
Ultimate analysis: C
17H
21ClN
2O
2
Theoretical value (%): C:63.65, H:6.60, N:8.73, Cl:11.05;
Measured value (%): C:63.59, H:6.63, N:8.74, Cl:11.03.
UV(MeOH)λ
max：214(ε38，222)，229(ε17，438)，282(ε13，405)。
IR(KCl)cm
-1：3219，2496(N-H)，3103，748(Ar?C-H)，2966，1428(C-H)，1692(C＝O)，1580，1525(Ar?C＝C)，1311，1128(C-N)，1033(C-O)。
1HNMR(DMSO-D
6)δ：2.10(d，2H，CH
2)，2.32(d，4H，CH
2)，2.52(m，2H，CH
2)，2.68(s，3H，CH
3)，3.88(s，2H，-CH)，5.14(s，H，CH)，8.03(m，H，CH)，8.08(d，H，CH)，10.81(s，H，HCl)，12.10(s，H，NH)。ESI-MS；EI?m/z：285(M+H，100％)，284(M
+，21.72％)。
Making with extra care of embodiment 4 Tropisetron hydrochlorides
(1) 50g Tropisetron hydrochloride crude product is dissolved in the 500ml water, slowly adds the sodium hydrogen carbonate solution of 8% (g/ml) then, stirring reaction to pH value of solution is 9, produces the tropisetron precipitation, filters, and 45 ℃ of drying under reduced pressure obtain tropisetron 42.2g.
(2) will go up the tropisetron 42.2g that obtains of step and be dissolved in the 300ml ethanol, and add the gac of 3.6g, stirring at room 40 minutes is filtered decarburization, collects filtrate.
(3) will go up the filtrate that obtains of step and utilize the preparative chromatography post to carry out separation and purification to obtain the Disodium phosphocreatine highly finished product, wherein to account for the methylene dichloride of moving phase 38% and pH that volume accounts for moving phase 62% as volume be 2 aqueous hydrochloric acid to the moving phase used of chromatographic column; Fixed phase stuffing is a silica gel; Flow velocity is 5.6ml/min; Column temperature: 25 ℃.Collect filtrate, drying under reduced pressure obtains purified Tropisetron hydrochloride 44.8g, yield 89.6%, and HPLC method purity is 99.9%.
Ultimate analysis: C
17H
21ClN
2O
2
Theoretical value (%): C:63.65, H:6.60, N:8.73, Cl:11.05;
Measured value (%): C:63.61, H:6.61, N:8.76, Cl:11.04.
UV(MeOH)λ
max：214(ε38，222)，229(ε17，438)，282(ε13，405)。
IR(KCl)cm
-1：3219，2496(N-H)，3103，748(Ar?C-H)，2966，1428(C-H)，1692(C＝O)，1580，1525(Ar?C＝C)，1311，1128(C-N)，1033(C-O)。
1HNMR(DMSO-D
6)δ：2.10(d，2H，CH
2)，2.32(d，4H，CH
2)，2.52(m，2H，CH
2)，2.68(s，3H，CH
3)，3.88(s，2H，-CH)，5.14(s，H，CH)，8.03(m，H，CH)，8.08(d，H，CH)，10.81(s，H，HCl)，12.10(s，H，NH)。ESI-MS；EI?m/z：285(M+H，100％)，284(M
+，21.72％)。
Making with extra care of embodiment 5 Tropisetron hydrochlorides
(1) 100g Tropisetron hydrochloride crude product is dissolved in the 500ml water, slowly adds the sodium carbonate solution of 12% (g/ml) then, stirring reaction to pH value of solution is 8, produces the tropisetron precipitation, filters, and 40 ℃ of drying under reduced pressure obtain tropisetron 84.1g.
(2) will go up the tropisetron 84.1g that obtains of step and be dissolved in the 400ml ethanol, and add the gac of 5.2g, stirring at room 40 minutes is filtered decarburization, collects filtrate.
(3) will go up the filtrate that obtains of step and utilize the preparative chromatography post to carry out separation and purification to obtain the Disodium phosphocreatine highly finished product, wherein to account for the methylene dichloride of moving phase 32% and pH that volume accounts for moving phase 68% as volume be 1 aqueous hydrochloric acid to the moving phase used of chromatographic column; Fixed phase stuffing is a silica gel; Flow velocity is 6.2ml/min; Column temperature: 25 ℃.Collect filtrate, drying under reduced pressure obtains purified Tropisetron hydrochloride 91.7g, yield 91.7%, and HPLC method purity is 99.9%.
Ultimate analysis: C
17H
21ClN
2O
2
Theoretical value (%): C:63.65, H:6.60, N:8.73, Cl:11.05;
Measured value (%): C:63.62, H:6.64, N:8.74, Cl:11.06.
UV(MeOH)λ
max：214(ε38，222)，229(ε17，438)，282(ε13，405)。
IR(KCl)cm
-1：3219，2496(N-H)，3103，748(Ar?C-H)，2966，1428(C-H)，1692(C＝O)，1580，1525(Ar?C＝C)，1311，1128(C-N)，1033(C-O)。
1HNMR(DMSO-D
6)δ：2.10(d，2H，CH
2)，2.32(d，4H，CH
2)，2.52(m，2H，CH
2)，2.68(s，3H，CH
3)，3.88(s，2H，-CH)，5.14(s，H，CH)，8.03(m，H，CH)，8.08(d，H，CH)，10.81(s，H，HCl)，12.10(s，H，NH)。ESI-MS；EI?m/z：285(M+H，100％)，284(M
+，21.72％)。
Claims (3)
1. the Tropisetron hydrochloride compound shown in the formula (I) comprises the steps:
(1) the Tropisetron hydrochloride crude product is soluble in water, slowly add alkali then, stirring reaction to pH value of solution is 7-10, generation tropisetron precipitation, filter, 35-50 ℃ of drying under reduced pressure obtains tropisetron, described alkali is sodium hydroxide, potassium hydroxide, yellow soda ash or sodium bicarbonate, preferred sodium hydroxide;
(2) will go up the tropisetron that obtains of step is dissolved in the solvent of 2-10 times of weight, the gac that adds overall solution volume 0.01-0.05 (g/ml), 20-50 ℃ was stirred 0.5-1.5 hour, filtered decarburization, collect filtrate, wherein said solvent is selected from propyl carbinol, normal hexane or ethanol;
(3) will go up the filtrate that obtains of step utilizes the preparative chromatography post to carry out separation and purification to obtain the Disodium phosphocreatine highly finished product, wherein the moving phase used of chromatographic column accounts for the methylene dichloride of moving phase 30-50% or acetone and volume as volume and accounts for the aqueous hydrochloric acid of the pH of moving phase 50-70% as 1-2, fixed phase stuffing is selected from silica gel or aluminum oxide, flow velocity is 4.5-6.8ml/min, column temperature 20-25 ℃, collect filtrate, drying under reduced pressure obtains the purified Tropisetron hydrochloride.
2. purification process according to claim 1 is characterized in that stirring reaction is to pH value of solution value 7-9 in the step (1).
3. purification process according to claim 1 is characterized in that adding in the step (2) gac of overall solution volume 0.02-0.03 (g/ml), whip attachment 30-50 minute.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101179171A CN101787021B (en) | 2010-03-05 | 2010-03-05 | High-purified tropisetron hydrochloride compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101179171A CN101787021B (en) | 2010-03-05 | 2010-03-05 | High-purified tropisetron hydrochloride compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101787021A true CN101787021A (en) | 2010-07-28 |
| CN101787021B CN101787021B (en) | 2011-08-24 |
Family
ID=42530414
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010101179171A Expired - Fee Related CN101787021B (en) | 2010-03-05 | 2010-03-05 | High-purified tropisetron hydrochloride compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101787021B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102351857A (en) * | 2011-08-23 | 2012-02-15 | 天津市汉康医药生物技术有限公司 | Tropiseiron hydrochloride compound |
| CN102367252A (en) * | 2011-11-03 | 2012-03-07 | 天津市汉康医药生物技术有限公司 | Tropisetron hydrochloride compound |
| CN102532128A (en) * | 2010-12-17 | 2012-07-04 | 北大方正集团有限公司 | Synthetic method of tropisetron and prepare method of hydrochloric acid tropisetron |
| CN103408543A (en) * | 2013-08-12 | 2013-11-27 | 回音必集团抚州制药有限公司 | High purity citric acid and navoban compound |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103159765B (en) * | 2011-12-15 | 2015-06-24 | 北京嘉林药业股份有限公司 | Indisetron purification method suitable for industrialization |
| CN104844591A (en) * | 2014-02-17 | 2015-08-19 | 中国医学科学院药物研究所 | Tropisetron hydrochloride crystal form II substance, preparation method, composition and uses thereof |
| CN104844592A (en) * | 2014-02-17 | 2015-08-19 | 中国医学科学院药物研究所 | Tropisetron hydrochloride crystal form III substance, preparation method, composition and uses thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101033225A (en) * | 2007-04-02 | 2007-09-12 | 北京成宇化工有限公司 | Process of preparing troipisetron |
-
2010
- 2010-03-05 CN CN2010101179171A patent/CN101787021B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101033225A (en) * | 2007-04-02 | 2007-09-12 | 北京成宇化工有限公司 | Process of preparing troipisetron |
Non-Patent Citations (3)
| Title |
|---|
| 《华西药学杂志》 20041231 刘宇等 止吐药盐酸托烷司琼的合成 433-434 1-3 第19卷, 第6期 2 * |
| 《山东医药工业》 20021231 刘宜辉等 盐酸托烷司琼的合成 5 1-3 第21卷, 第1期 2 * |
| 《湖南师范大学学报(医学版)》 20061231 向红琳等 盐酸托烷司琼的合成工艺改进 29-30 1-3 第3卷, 第4期 2 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102532128A (en) * | 2010-12-17 | 2012-07-04 | 北大方正集团有限公司 | Synthetic method of tropisetron and prepare method of hydrochloric acid tropisetron |
| CN102532128B (en) * | 2010-12-17 | 2014-11-12 | 北大方正集团有限公司 | Synthetic method of tropisetron and prepare method of hydrochloric acid tropisetron |
| CN102351857A (en) * | 2011-08-23 | 2012-02-15 | 天津市汉康医药生物技术有限公司 | Tropiseiron hydrochloride compound |
| CN102351857B (en) * | 2011-08-23 | 2013-06-12 | 天津市汉康医药生物技术有限公司 | Tropiseiron hydrochloride compound |
| CN102367252A (en) * | 2011-11-03 | 2012-03-07 | 天津市汉康医药生物技术有限公司 | Tropisetron hydrochloride compound |
| CN103408543A (en) * | 2013-08-12 | 2013-11-27 | 回音必集团抚州制药有限公司 | High purity citric acid and navoban compound |
| CN103408543B (en) * | 2013-08-12 | 2014-02-12 | 回音必集团抚州制药有限公司 | High purity citric acid and navoban compound |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101787021B (en) | 2011-08-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101787021B (en) | High-purified tropisetron hydrochloride compound | |
| CN101440063B (en) | Preparation of piperaquini phosphatis | |
| EP3828170A1 (en) | Method for safely preparing pimavanserin and tartrate salt thereof using triphosgene | |
| CN101798314B (en) | High-purity cefmenoxime hydrochloride compound | |
| CN103435538B (en) | (R) preparation method of-3-amido piperidine hydrochlorate | |
| AU698595B2 (en) | 3-phenylisoquinol-1(2H)-one derivatives, their preparation and their therapeutic application | |
| CN103172644A (en) | Method for preparing medicinal artemisinin | |
| CN104231016B (en) | A kind of preparation method of Etimicin sulfate. | |
| CN102584815A (en) | Method for preparing tropisetron hydrochloride on large scale | |
| CN116621810A (en) | Process for preparing 2-methyl nicotine | |
| CN102492020B (en) | Pidotimod compound and new preparation method thereof | |
| CN103183708A (en) | Preparation method for fosaprepitant dimeglumine | |
| CN103172645A (en) | High-efficiency synthesis method of artemisinin | |
| CN102603594B (en) | Preparation method of (S)-oxiracetam | |
| CN102030693B (en) | Acetylcysteine compound and novel method thereof | |
| CN101891755B (en) | Cefsulodin sodium compound and novel preparation method thereof | |
| CN102659884A (en) | Gemcitabine hydrochloride purifying method | |
| CN102603595A (en) | Preparation method of (S)-oxiracetam | |
| CN101768164B (en) | Naloxone hydrochloride compound with high purity | |
| CN106117244A (en) | The process for purification of Cefditoren pivoxil Cephalosporins | |
| CN108033962B (en) | A method of synthesis (6S) -5-methyltetrahydrofolate salt | |
| CN102010433A (en) | Cefepime hydrochloride compound and new preparation method thereof | |
| CN102127134B (en) | Ribavirin compound and novel preparation method thereof | |
| CN102558189B (en) | Refining method of methyhaaltrexone bromide | |
| CN104086486A (en) | Preparation method of dimemorfan phosphate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Hainan Lingkang Pharmaceutical Co., Ltd. Assignor: Wang Ming Contract record no.: 2011990000939 Denomination of invention: High-purified tropisetron hydrochloride compound Granted publication date: 20110824 License type: Exclusive License Open date: 20100728 Record date: 20110928 |
|
| ASS | Succession or assignment of patent right |
Owner name: HAINAN LINGKANG PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: WANG MING Effective date: 20130724 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 570125 HAIKOU, HAINAN PROVINCE TO: 570216 HAIKOU, HAINAN PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20130724 Address after: 570216 Hainan Province, Haikou city Jinpan Industrial Development Zone Industrial Village No. 3-6 building Patentee after: Hainan Lingkang Pharmaceutical Co., Ltd. Address before: The new business building No. 48 570125 Hainan city of Haikou province China World Trade Center Road, room 2601 Patentee before: Wang Ming |
|
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20110824 Termination date: 20160305 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |