CN103232389A - Preparation method of 2-chloromethyl-4-methoxyl-3,5-dimethyl pyridine hydrochloride - Google Patents
Preparation method of 2-chloromethyl-4-methoxyl-3,5-dimethyl pyridine hydrochloride Download PDFInfo
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- CN103232389A CN103232389A CN2013101663892A CN201310166389A CN103232389A CN 103232389 A CN103232389 A CN 103232389A CN 2013101663892 A CN2013101663892 A CN 2013101663892A CN 201310166389 A CN201310166389 A CN 201310166389A CN 103232389 A CN103232389 A CN 103232389A
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- methoxyl group
- chloromethyl
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- methoxyl
- lutidine
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- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- LCJDHJOUOJSJGS-UHFFFAOYSA-N 2-(chloromethyl)-4-methoxy-3,5-dimethylpyridin-1-ium;chloride Chemical compound Cl.COC1=C(C)C=NC(CCl)=C1C LCJDHJOUOJSJGS-UHFFFAOYSA-N 0.000 title abstract 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 45
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 27
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229960000344 thiamine hydrochloride Drugs 0.000 claims description 13
- 235000019190 thiamine hydrochloride Nutrition 0.000 claims description 13
- 239000011747 thiamine hydrochloride Substances 0.000 claims description 13
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 claims description 13
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-Lutidine Substances CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 claims description 12
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims description 6
- 230000006837 decompression Effects 0.000 claims description 5
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 5
- 238000012544 monitoring process Methods 0.000 claims description 5
- 230000002378 acidificating effect Effects 0.000 abstract description 2
- PSEPRWKZZJWRCB-UHFFFAOYSA-N (4-methoxy-3,5-dimethylpyridin-2-yl)methanol Chemical compound COC1=C(C)C=NC(CO)=C1C PSEPRWKZZJWRCB-UHFFFAOYSA-N 0.000 abstract 1
- 239000012295 chemical reaction liquid Substances 0.000 abstract 1
- 238000001035 drying Methods 0.000 abstract 1
- 239000002904 solvent Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 229960000381 omeprazole Drugs 0.000 description 3
- ZBFDAUIVDSSISP-UHFFFAOYSA-N 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methylsulfinyl]-1H-imidazo[4,5-b]pyridine Chemical compound N=1C2=NC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C ZBFDAUIVDSSISP-UHFFFAOYSA-N 0.000 description 2
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- SUBDBMMJDZJVOS-DEOSSOPVSA-N esomeprazole Chemical compound C([S@](=O)C1=NC2=CC=C(C=C2N1)OC)C1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-DEOSSOPVSA-N 0.000 description 2
- 229960004770 esomeprazole Drugs 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 229950008375 tenatoprazole Drugs 0.000 description 2
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- GGRLKHMFMUXIOG-UHFFFAOYSA-M 2-acetyloxyethyl(trimethyl)azanium;hydroxide Chemical compound [OH-].CC(=O)OCC[N+](C)(C)C GGRLKHMFMUXIOG-UHFFFAOYSA-M 0.000 description 1
- CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 102100021977 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Human genes 0.000 description 1
- 108050004000 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229940125864 PPI inhibitor Drugs 0.000 description 1
- 108010079943 Pentagastrin Proteins 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- -1 methoxyl group Chemical group 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000007383 nerve stimulation Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- ANRIQLNBZQLTFV-DZUOILHNSA-N pentagastrin Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1[C]2C=CC=CC2=NC=1)NC(=O)CCNC(=O)OC(C)(C)C)CCSC)C(N)=O)C1=CC=CC=C1 ANRIQLNBZQLTFV-DZUOILHNSA-N 0.000 description 1
- 229960000444 pentagastrin Drugs 0.000 description 1
- 208000000689 peptic esophagitis Diseases 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- GGWBHVILAJZWKJ-KJEVSKRMSA-N ranitidine hydrochloride Chemical compound [H+].[Cl-].[O-][N+](=O)\C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 GGWBHVILAJZWKJ-KJEVSKRMSA-N 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 210000001186 vagus nerve Anatomy 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a preparation method of 2-chloromethyl-4-methoxyl-3,5-dimethyl pyridine hydrochloride. The preparation method sequentially comprises the following steps of: dissolving 2-hydroxymethyl-4-methoxyl-3,5-dimethyl pyridine into toluene; adding a toluene solution of triphosgene dropwise at 0 to 10 DEG C; after the reaction is finished, adding a small amount of methanol dropwise; removing acidic gas under reduced pressure; and centrifuging and drying the reaction liquid to obtain the 2-chloromethyl-4-methoxyl-3,5-dimethyl pyridine hydrochloride. The preparation method of the 2-chloromethyl-4-methoxyl-3,5-dimethyl pyridine hydrochloride has the advantages of simpleness in operation, high yield, high purity and few three wastes.
Description
Technical field
The present invention relates to proton pump inhibitor key intermediate 2-chloromethyl-4-methoxyl group-3, the preparation method of 5-dimethyl pyrazole thiamine hydrochloride.
Background technology
2-chloromethyl-4-methoxyl group-3,5-dimethyl pyrazole thiamine hydrochloride is mainly used in organic synthesis, and 2 chloromethyl and other reagent (as sulfydryl, amino, phenol etc.) reaction obtains various derivatives.Its derivative such as omeprazole [Omeprazole; chemistry 5-methoxyl group by name-2-{[(4-methoxyl group-3; 5-dimethyl-2 pyridine) methyl] sulfinyl-the 1H-benzoglyoxaline-], levo-omeprazole (esomeprazole; Esomeprazole), tenatoprazole (Tenatoprazole; chemistry 5-methoxyl group-2-(4-methoxyl group-3,5-lutidine-2-methylsulfinyl) imidazo by name (4,5-b) pyridine) etc.These PPI inhibitor chemical stabilities are good, and the gastric acid secretion that histamine, pentagastrin, vagusstoff, food and vagus nerve stimulation etc. are caused all has strong and lasting restraining effect.Aspect the treatment digestive tract ulcer, compare H
2The effect of receptor antagonist such as Cimitidine Type A/AB and Ranitidine HCL is better, has rapid alleviating pain, short treating period, advantage that the pathology healing rate is high.This medicine does not have severe side effect, and tolerance is good, is applicable to treatment gastric and duodenal ulcer, reflux esophagitis, Zhuo-Emhorn syndromes, is medicine commonly used in the acid inhibitor of having found at present.
Synthetic (WO2012024620) that it also is used for oneself the plain inhibitor of chemotactic (autotaxin inhibitors) is used for the treatment of chronic inflammatory diseases, autoimmune disease, fibrotic disease, sacred disease and tumor disease etc.
2-chloromethyl-4-methoxyl group-3,5-dimethyl pyrazole thiamine hydrochloride is synthesizing heterocyclic compounds important intermediate, existing synthetic method substantially all is to be solvent with haloalkane (methylene dichloride, chloroform), sulfur oxychloride is chlorizating agent, reaction boils off solvent after finishing, add another kind of solvent (mixed solvent of acetone, Virahol, ethyl acetate or itself and sherwood oil, ether) again, filter, dry salable product, yield 86 ~ 92.7%(DE3840372; ES2024357; CN101648907; Fine chemistry industry, 2004,21 (1): 67-69; Chinese Journal of Pharmaceuticals, 2004,35 (5): 261-262; The Shanxi chemical industry, 2005,25 (4): 9-10).All to boil off reaction solvent in these methods, add another kind of crystallization or dispersed solvent again, product perishable (mainly be that methoxyl group demethylation under acidic conditions in 4-position becomes phenol, impurity (III) structure is as follows) in the still-process can cause yield low and product is defective.And solvent recovering rate is low, causes bigger pollution.
Also be to be that solvent, sulfur oxychloride are to add methyl alcohol after reagent, reaction finish to remove the suspension that excessive sulfur oxychloride obtains product with toluene among the WO2004035565.Do not mention aftertreatment in the patent.Owing in the suspension more sour gas is arranged, separation yield is descended greatly, there is more hydrochloride to exist in the mother liquor with the oily situation.
And in the above document chlorination reagent all usefulness be sulfur oxychloride, emit a large amount of sulfurous gas in the reaction process, smell is heavier.
Summary of the invention
The purpose of this invention is to provide a kind of simple to operate, the three wastes are few, have the 2-chloromethyl-4-methoxyl group-3 of stronger industrial application value, the preparation method of 5-dimethyl pyrazole thiamine hydrochloride, the product yield height of gained, purity height.
2-chloromethyl of the present invention-4-methoxyl group-3, the preparation method of 5-dimethyl pyrazole thiamine hydrochloride, step is as follows:
With 2-methylol-4-methoxyl group-3, the 5-lutidine is dissolved in the toluene, the preparation mass concentration is 2-methylol-4-methoxyl group-3 of 20%～30%, the toluene solution of 5-lutidine, drip the toluene solution that mass concentration is 40%～50% triphosgene at 0～10 ℃, 2-methylol-4-methoxyl group-3, the mol ratio of 5-lutidine and triphosgene is 1:0.35～0.37, high performance liquid chromatography monitoring reaction, after reaction finishes, drip methyl alcohol, 2-methylol-4-methoxyl group-3, the mol ratio of 5-lutidine and methyl alcohol are 1:0.10～0.25, and sour gas is sloughed in decompression then, reaction solution is through centrifugal, oven dry obtains 2-chloromethyl-4-methoxyl group-3,5-dimethyl pyrazole thiamine hydrochloride.
Concrete synthetic route is as follows:
Structural formula (
) be 2-chloromethyl-4-methoxyl group-3,5-dimethyl pyrazole thiamine hydrochloride; The structure formula II is 2-methylol-4-methoxyl group-3, the 5-lutidine.
Preparation method of the present invention is simple to operate, and the three wastes are few, is triphosgene with the chlorination reagent, emits carbonic acid gas in the reaction process, more is conducive to environmental protection, and product yield can reach more than 96.0%, the purity height.
Embodiment
Example 1
Drop in the there-necked flask of 1000ml toluene (320.0g, 370mL), 2-methylol-4-methoxyl group-3, the 5-lutidine (80.0g, 480mmol), stirring and dissolving.(49.8g is 168mmol) with toluene (74.7g, mixing solutions 86mL) for 10 ℃ of dropping triphosgene (BTC), added the back stirring at room 3 hours, high performance liquid chromatography monitoring reaction is after reaction finishes, drip methyl alcohol (1.5g, 48mmol), stirred 1 hour, be cooled to 5 ℃, sour gas is sloughed in decompression, it is 2-chloromethyl-4-methoxyl group-3 of 99.74% that reaction solution obtains content through centrifugal, oven dry, 5-dimethyl pyrazole thiamine hydrochloride (105.6g, yield 97.51%).
Example 2
Drop in the there-necked flask of 1000ml toluene (240.0g, 277mL), 2-methylol-4-methoxyl group-3, the 5-lutidine (80.0g, 480mmol), stirring and dissolving.(51.3g is 172mmol) with toluene (62.7g, mixing solutions 72mL) for 5 ℃ of dropping triphosgene (BTC), added the back stirring at room 3 hours, high performance liquid chromatography monitoring reaction is after reaction finishes, drip methyl alcohol (3.1g, 96mmol), stirred 1 hour, be cooled to 5 ℃, sour gas is sloughed in decompression, it is 2-chloromethyl-4-methoxyl group-3 of 99.83% that reaction solution obtains content through centrifugal, oven dry, 5-dimethyl pyrazole thiamine hydrochloride (105.8g, yield 97.79%).
Example 3
Drop in the there-necked flask of 1000ml toluene (186.0g, 215mL), 2-methylol-4-methoxyl group-3, the 5-lutidine (80.0g, 480mmol), stirring and dissolving.(52.8g is 178mmol) with toluene (52.8g, mixing solutions 61mL) for 0 ℃ of dropping triphosgene (BTC), added the back stirring at room 3 hours, high performance liquid chromatography monitoring reaction is after reaction finishes, drip methyl alcohol (3.8g, 120mmol), stirred 1 hour, be cooled to 5 ℃, sour gas is sloughed in decompression, it is 2-chloromethyl-4-methoxyl group-3 of 99.88% that reaction solution obtains content through centrifugal, oven dry, 5-dimethyl pyrazole thiamine hydrochloride (105.6g, yield 97.70%).
Claims (1)
1.2-chloromethyl-4-methoxyl group-3, the preparation method of 5-dimethyl pyrazole thiamine hydrochloride, step is as follows:
With 2-methylol-4-methoxyl group-3, the 5-lutidine is dissolved in the toluene, the preparation mass concentration is 2-methylol-4-methoxyl group-3 of 20%～30%, the toluene solution of 5-lutidine, drip the toluene solution that mass concentration is 40%～50% triphosgene at 0～10 ℃, 2-methylol-4-methoxyl group-3, the mol ratio of 5-lutidine and triphosgene is 1:0.35～0.37, high performance liquid chromatography monitoring reaction, after reaction finishes, drip methyl alcohol, 2-methylol-4-methoxyl group-3, the mol ratio of 5-lutidine and methyl alcohol are 1:0.10～0.25, and sour gas is sloughed in decompression then, reaction solution is through centrifugal, oven dry obtains 2-chloromethyl-4-methoxyl group-3,5-dimethyl pyrazole thiamine hydrochloride.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2013101663892A CN103232389A (en) | 2013-05-08 | 2013-05-08 | Preparation method of 2-chloromethyl-4-methoxyl-3,5-dimethyl pyridine hydrochloride |
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| CN2013101663892A CN103232389A (en) | 2013-05-08 | 2013-05-08 | Preparation method of 2-chloromethyl-4-methoxyl-3,5-dimethyl pyridine hydrochloride |
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| CN2013101663892A Pending CN103232389A (en) | 2013-05-08 | 2013-05-08 | Preparation method of 2-chloromethyl-4-methoxyl-3,5-dimethyl pyridine hydrochloride |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103664750A (en) * | 2013-12-09 | 2014-03-26 | 惠州市莱佛士制药技术有限公司 | Synthetic method of prazole chloride |
| CN107011252A (en) * | 2017-06-09 | 2017-08-04 | 浙江工业大学 | The method for drawing azole intermediate and medicine is prepared using the green technology for substituting the poisonous and harmful substances such as phosgene, thionyl chloride |
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| US20050038076A1 (en) * | 2003-07-15 | 2005-02-17 | Garst Michael E. | Process for preparing isomerically pure prodrugs of proton pump inhibitors |
| US20080004447A1 (en) * | 2002-10-18 | 2008-01-03 | Anders Gustavsson | Method for the Synthesis of a Benzimidazole Compound |
| CN100374423C (en) * | 2001-12-11 | 2008-03-12 | 西巴特殊化学品控股有限公司 | Process for the preparation of 4-methyl-7-aminoquinolones |
| CN102887886A (en) * | 2012-10-26 | 2013-01-23 | 扬子江药业集团江苏海慈生物药业有限公司 | Preparation method of pantoprazole sodium |
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2013
- 2013-05-08 CN CN2013101663892A patent/CN103232389A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100374423C (en) * | 2001-12-11 | 2008-03-12 | 西巴特殊化学品控股有限公司 | Process for the preparation of 4-methyl-7-aminoquinolones |
| US20080004447A1 (en) * | 2002-10-18 | 2008-01-03 | Anders Gustavsson | Method for the Synthesis of a Benzimidazole Compound |
| US20050038076A1 (en) * | 2003-07-15 | 2005-02-17 | Garst Michael E. | Process for preparing isomerically pure prodrugs of proton pump inhibitors |
| CN102887886A (en) * | 2012-10-26 | 2013-01-23 | 扬子江药业集团江苏海慈生物药业有限公司 | Preparation method of pantoprazole sodium |
Non-Patent Citations (1)
| Title |
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| 宋伟国: "泮托拉唑钠合成工艺研究", 《山东大学硕士学位论文》, 15 August 2008 (2008-08-15) * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103664750A (en) * | 2013-12-09 | 2014-03-26 | 惠州市莱佛士制药技术有限公司 | Synthetic method of prazole chloride |
| CN107011252A (en) * | 2017-06-09 | 2017-08-04 | 浙江工业大学 | The method for drawing azole intermediate and medicine is prepared using the green technology for substituting the poisonous and harmful substances such as phosgene, thionyl chloride |
| CN107011252B (en) * | 2017-06-09 | 2018-06-08 | 浙江工业大学 | The method for drawing azole intermediate and drug is prepared using the green technology for substituting the poisonous and harmful substances such as phosgene, thionyl chloride |
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Application publication date: 20130807 |