CN106892885A - A kind of method for synthesizing ranitidine - Google Patents
A kind of method for synthesizing ranitidine Download PDFInfo
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- CN106892885A CN106892885A CN201710267791.8A CN201710267791A CN106892885A CN 106892885 A CN106892885 A CN 106892885A CN 201710267791 A CN201710267791 A CN 201710267791A CN 106892885 A CN106892885 A CN 106892885A
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
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Abstract
A kind of method for synthesizing ranitidine, comprises the following steps：1）At 30~35 DEG C vinylidene chloride is reacted to obtain to dropwise addition sodium hydrate aqueous solution in 1,1,2 trichloroethanes；1,1,2 trichloroethanes are 1 with the mass ratio of NaOH:0.3~0.33；2）To vinylidene chloride is added dropwise in the mixed acid of concentrated hydrochloric acid and concentrated nitric acid at 20~25 DEG C, react 2~4 hours；Vinylidene chloride is 1 with the amount ratio of mixed acid:2~3；3）In NaOH or potassium hydroxide aqueous solution, Mercaptamine is added, then step 2 is added dropwise at 50~55 DEG C）Product obtains cyclization product；4）Cyclization product and methylamine are reacted 14~18 hours at room temperature in ethanol or methanol solution and obtains open-loop products；5）Open-loop products and 2 [(dimethylamino) methyl] 5 chloromethylfurans are added into potassium hydroxide or sodium hydrate aqueous solution, ranitidine is obtained within 2 ~ 4 hours in 40 ~ 50 DEG C of reactions.Present approach reduces potential safety hazard, simply, it is easy to industrialized production.
Description
Technical field
The present invention relates to the field of chemical synthesis, and in particular to a kind of method of synthesis ranitidine.
Background technology
Ranitidine hydrochloride (Ranitidine hydrochloride), chemical entitled N'- methyl-N- [2 [[5- [(diformazans
Amino) methyl -2- furyls] methyl] thio] ethyl] -2- nitro -1,1- ethylene diamine hydrochlorides are a kind of histamine H2-receptors
Blocking agent, can suppress basal gastric acid secretion and post-stimulatory gastric acid secretion, may also suppress the secretion of pepsin.By Ge Lan element histories
Gram company lists in nineteen eighty-three, after listing clinical efficacy preferably, so while there is the history of more than 30 years, but still in state
Interior or foreign countries all sell well.
Due to the increasingly raising of living standards of the people, disease of digestive system is one of common frequently-occurring disease, wherein and to disappear
Based on Peptic-ulcer, mainly because smoking, drink, nervous, medicine irritation causes, it is total that the gastrointestinal disease incidence of disease accounts for population
Several 10~20%.With the development of society, the quickening of rhythm of life, the incidence of disease of gastrointestinal disease also have year by year it is elevated become
Gesture, the pharmaceutical market of such disease also by steady-state growth, ranitidine hydrochloride as old brand Digestive system surgical procedures, because of its price
Low, good effect, still by market be widely popularized and use,
Traditional ranitidine hydrochloride synthesis technique is condensed instead from nitromethane synthesis side chain and then with furan segments
Should, finally formed into salt, but the raw material that synthesis side chain need to be exploded using this easy firing of nitromethane, and last condensation reaction
When can produce substantial amounts of methyl mercaptan gas, it is very serious to atmosphere pollution.More safety and environmental protection produces high quality processed
Product is the target that we constantly pursue, and this time the whole building-up process raw material of ranitidine new technology of research and development is all cheap and easy to get
And the hidden danger without security, methyl mercaptan gas will not be produced, prospect with industrialized production more environmentally-friendly to environment.
Conventional synthesis route is as follows：
The original with severe odors and severe toxicity such as carbon disulfide, dimethyl suflfate is needed to use in traditional synthesis
Material, and can produce methyl mercaptan gas in two fragment condensations, be also the gas for having severe odors, and thus traditional handicraft is neither
Safety, environmental pollution is also very serious.
The content of the invention
To solve above-mentioned problems of the prior art, the present invention provides a kind of method of new synthesis ranitidine.
The technical solution adopted by the present invention is that a kind of method for synthesizing ranitidine comprises the following steps：
(1) vinylidene chloride is synthesized：
With 1,1,2- trichloroethanes is raw material, sodium hydrate aqueous solution reaction is added dropwise under the conditions of 30~35 DEG C and obtains inclined two
Vinyl chloride；The 1,1,2- trichloroethanes is 1 with the mass ratio of NaOH:0.3~0.33；
(2) synthesis of the chloro- 2- nitroethylenes of 1,1- bis-：
By concentrated hydrochloric acid and concentrated nitric acid with mass ratio 1:1~1.2 is mixed into mixed acid；In at 20~25 DEG C to the mixed acid
It is middle that the vinylidene chloride that step (1) is obtained is added dropwise, after reacting 2~4 hours, extracted with chloroform or dichloromethane after adding water, washing,
Dry, filter, being concentrated to give the chloro- 2- nitroethylenes of 1,1- bis-；The vinylidene chloride is 1 with the mass ratio of mixed acid:2~3；
(3) ring closure reaction：
In NaOH or potassium hydroxide aqueous solution, Mercaptamine is added, step (2) is added dropwise at 50~55 DEG C
The chloro- 2- nitroethylenes of 1,1- bis- for obtaining, reaction is extracted with chloroform or dichloromethane after 1~2 hour, dries, filters, being concentrated to give
To cyclization product；Described NaOH or potassium hydroxide and the mol ratio of the chloro- 2- nitroethylenes of 1,1- bis- are 4~4.5:1；
(4) ring-opening reaction
Step (3) gained cyclization product is reacted 14~18 hours at room temperature with methylamine in ethanol or methyl alcohol, filtering,
It is recrystallized to give open-loop products；The cyclization product is 1 with the mole ratio of methylamine:2~2.2；
(5) synthesis of ranitidine
By step (4) gained open-loop products and 2- [(dimethylamino) methyl] -5 Chloromethyl-furans add potassium hydroxide or
Sodium hydrate aqueous solution, in 40~50 DEG C, reaction is concentrated under reduced pressure after 2~4 hours, recrystallization, filtering, cooling, crystallization, dry
To ranitidine；Described potassium hydroxide or NaOH and the mol ratio of open-loop products are 1.1~1.3:1.
Further, the naoh concentration described in step (1) is preferably NaOH mass fraction 30%.
Further, 1,1,2- trichloroethanes described in step (1) is preferably 1 with the mass ratio of NaOH:0.3.
Further, step (2) and the extraction described in step (3) preferably uses chloroform extraction.
Further, the washing described in step (2) is to be washed with 5% sodium bicarbonate solution；Described drying is with nothing
Water magnesium sulfate is dried.
Further, the vinylidene chloride described in step (2) is preferably 1 with the mass ratio of mixed acid:2.5；Step (3) institute
The NaOH or potassium hydroxide stated are preferably 4.2 with the mol ratio of the chloro- 2- nitroethylenes of 1,1- bis-:1；Described in step (4)
Cyclization product is preferably 1 with the mol ratio of methylamine:2.1；Potassium hydroxide or NaOH and open-loop products described in step (5)
Mol ratio is preferably 1.2:1.
Further, step (3) described drying is to be dried with anhydrous magnesium sulfate.
Further, the recrystallization described in step (4) is to use ethyl alcohol recrystallization.
Further, the recrystallization described in step (5) is using ethanol or recrystallisation from isopropanol.
Synthetic route of the present invention is
The synthetic method that the present invention is provided, employs cheap and easy to get 1, and 1,2- trichloroethanes passes through as initiation material
Elimination, nitrification, cyclization, open loop, condensation reaction obtain final products ranitidine, do not have heavy odor in whole building-up process
Raw material, intermediate and accessory substance, do not use extremely toxic substance, and reaction condition is gentle, reduces potential safety hazard, simply, is easy to work
Industry metaplasia is produced, and is one safe and environmentally friendly, meets the green syt route of modern pharmaceutical industry theory.
Brief description of the drawings
Fig. 1 is the ranitidine 1H spectrograms prepared by the present invention.
Fig. 2 is the ranitidine 13C spectrograms prepared by the present invention.
Specific embodiment
Embodiment 1：
(1) synthesis of vinylidene chloride
The trichloroethanes of 100g 1,1,2- is added in the four-hole bottle equipped with distilling apparatus, feed liquid is heated to 30~35 DEG C,
30% sodium hydroxide solution 100g is added dropwise with constant pressure funnel, dropwise addition process constantly has liquid to be distilled device condensation reception,
Obtain vinylidene chloride 70g, yield：96%, GC purity>95%.
(2) synthesis of the chloro- 2- nitroethylenes of 1,1- bis-
80g concentrated hydrochloric acids and 80g concentrated nitric acids are added in there-necked flask, control temperature is added dropwise vinylidene chloride at 20~25 DEG C
60g, drips off continuation insulation reaction 3 hours, and reaction is poured into 100g frozen water after terminating, and adds the extraction of 100g chloroforms, collects chloroform
Layer and the sodium bicarbonate solution with 5% wash twice, the chloroform after washing with anhydrous magnesium sulfate dry 1 hour, filtering, be concentrated to give
1,1- bis- chloro- 2- nitroethylenes 80g, yield：91%, GC purity>95%.
(3) ring closure reaction
63g NaOH and 300g water are added in there-necked flask, 42g Mercaptamines is added after solid is entirely molten, so
After be warming up to 50~55 DEG C at the chloro- 2- nitroethylenes 50g of 1,1- bis- are added dropwise, drip off insulation reaction 1 hour, be down to room temperature, use
300g*2 chloroforms are extracted twice, are dried 1 hour with anhydrous magnesium sulfate, and filtering is concentrated to give cyclization product 45g, yield：87%, GC
Purity>92%.
(4) ring-opening reaction
30g cyclizations product and 100g ethanol are added in there-necked flask, 30% methylethylolamine solution 43g are added dropwise at room temperature,
Drip follow-up continuous insulation reaction 16 hours, reaction is filtered after terminating, gained tide product directly obtain open-loop products with ethyl alcohol recrystallization
32g, yield：89%, purity>95%.
(5) synthesis of ranitidine
Added in there-necked flask 100g water, 30g open-loop products, 30g2- [(dimethylamino) methyl] -5 Chloromethyl-furans and
12g potassium hydroxide, then heats to 40~50 DEG C, and insulation reaction 2 hours is concentrated under reduced pressure at 50~60 DEG C by water after having reacted
It is dry, 50g ethanol is subsequently adding, 40~50 DEG C are heated to, filtering, filtrate is cooled to -5~0 DEG C of insulation and crystallizes 4 hours, and filtering is done
It is dry to obtain ranitidine 45g, yield：85%, purity>99%.
Embodiment 2：
(1) synthesis of vinylidene chloride
The trichloroethanes of 100g 1,1,2- is added in the four-hole bottle equipped with distilling apparatus, feed liquid 30 DEG C is heated to, with perseverance
Pressure dropping funel is added dropwise 30% sodium hydroxide solution 110g, and dropwise addition process constantly has liquid to be distilled device condensation reception, obtains partially
Dichloroethylene.
(2) synthesis of the chloro- 2- nitroethylenes of 1,1- bis-
62g concentrated hydrochloric acids and 68g concentrated nitric acids are added in there-necked flask, control temperature is added dropwise vinylidene chloride 65g at 20 DEG C,
Drip off continuation insulation reaction 2 hours, reaction is poured into 100g frozen water after terminating, add the extraction of 100g dichloromethane, collect dichloro
Methane layer and the sodium bicarbonate solution with 5% wash twice, the dichloromethane after washing with anhydrous magnesium sulfate dry 1 hour, mistake
Filter, is concentrated to give the chloro- 2- nitroethylenes of 1,1- bis-.
(3) ring closure reaction
79g potassium hydroxide and 300g water are added in there-necked flask, 42g Mercaptamines is added after solid is entirely molten, so
After be warming up to 50 DEG C at the chloro- 2- nitroethylenes 50g of 1,1- bis- are added dropwise, drip off insulation reaction 2 hours, be down to room temperature, use 300g*2
Dichloromethane is extracted twice, is dried 1 hour with anhydrous magnesium sulfate, and filtering is concentrated to give cyclization product.
(4) ring-opening reaction
30g cyclizations product and 100g methyl alcohol are added in there-necked flask, 30% methylamine methanol solution is added dropwise at room temperature
42.5g, drips follow-up continuous insulation reaction 14 hours, and reaction is filtered after terminating, and gained tide product must directly be opened with ethyl alcohol recrystallization
Ring product.
(5) synthesis of ranitidine
Added in there-necked flask 100g water, 30g open-loop products, 30g2- [(dimethylamino) methyl] -5 Chloromethyl-furans and
7.5g NaOH, then heats to 40 DEG C, and insulation reaction 3 hours is concentrated under reduced pressure dry at 50~60 DEG C by water after having reacted, so
50g ethanol is added afterwards, 40~50 DEG C are heated to, and filtering, filtrate is cooled to -5~0 DEG C of insulation and crystallizes 4 hours, filtering, dry
Ranitidine.
Embodiment 3：
(1) synthesis of vinylidene chloride
The trichloroethanes of 100g 1,1,2- is added in the four-hole bottle equipped with distilling apparatus, feed liquid 35 DEG C is heated to, with perseverance
Pressure dropping funel is added dropwise 30% sodium hydroxide solution 100g, and dropwise addition process constantly has liquid to be distilled device condensation reception, obtains partially
Dichloroethylene.
(2) synthesis of the chloro- 2- nitroethylenes of 1,1- bis-
82g concentrated hydrochloric acids and 98g concentrated nitric acids are added in there-necked flask, control temperature is added dropwise vinylidene chloride at 20~25 DEG C
60g, drips off continuation insulation reaction 4 hours, and reaction is poured into 100g frozen water after terminating, and adds the extraction of 100g chloroforms, collects chloroform
Layer and the sodium bicarbonate solution with 5% wash twice, the chloroform after washing with anhydrous magnesium sulfate dry 1 hour, filtering, be concentrated to give
The chloro- 2- nitroethylenes of 1,1- bis-.
(3) ring closure reaction
59g NaOH and 300g water are added in there-necked flask, 42g Mercaptamines is added after solid is entirely molten, so
After be warming up to 55 DEG C at the chloro- 2- nitroethylenes 50g of 1,1- bis- are added dropwise, drip off insulation reaction 1 hour, be down to room temperature, use 300g*2
Chloroform is extracted twice, is dried 1 hour with anhydrous magnesium sulfate, and filtering is concentrated to give cyclization product.
(4) ring-opening reaction
30g cyclizations product and 100g ethanol are added in there-necked flask, 30% methylethylolamine solution is added dropwise at room temperature
44.5g, drips follow-up continuous insulation reaction 18 hours, and reaction is filtered after terminating, and gained tide product must directly be opened with ethyl alcohol recrystallization
Ring product.
(5) synthesis of ranitidine
Added in there-necked flask 100g water, 30g open-loop products, 30g2- [(dimethylamino) methyl] -5 Chloromethyl-furans and
11.4g potassium hydroxide, then heats to 50 DEG C, and insulation reaction 4 hours is concentrated under reduced pressure dry at 50~60 DEG C by water after having reacted,
50g ethanol is subsequently adding, 40~50 DEG C are heated to, filtering, filtrate is cooled to -5~0 DEG C of insulation and crystallizes 4 hours, and filtering is dried
Obtain ranitidine.
Embodiment 4：
(1) synthesis of vinylidene chloride
The trichloroethanes of 100g 1,1,2- is added in the four-hole bottle equipped with distilling apparatus, feed liquid 33 DEG C is heated to, with perseverance
Pressure dropping funel is added dropwise 30% sodium hydroxide solution 100g, and dropwise addition process constantly has liquid to be distilled device condensation reception, obtains partially
Dichloroethylene.
(2) synthesis of the chloro- 2- nitroethylenes of 1,1- bis-
75g concentrated hydrochloric acids and 75g concentrated nitric acids are added in there-necked flask, control temperature is added dropwise vinylidene chloride 60g at 23 DEG C,
Drip off continuation insulation reaction 3 hours, reaction is poured into 100g frozen water after terminating, add the extraction of 100g chloroforms, collect chloroform layer simultaneously
Washed twice with 5% sodium bicarbonate solution, the chloroform after washing is dried 1 hour with anhydrous magnesium sulfate, filtering is concentrated to give 1,1-
Two chloro- 2- nitroethylenes.
(3) ring closure reaction
63.4g NaOH and 300g water are added in there-necked flask, 42g Mercaptamines are added after solid is entirely molten,
The chloro- 2- nitroethylenes 50g of 1,1- bis- are added dropwise at then heating to 53 DEG C, insulation reaction is dripped off 1 hour, room temperature is down to, 300g* is used
2 chloroforms are extracted twice, are dried 1 hour with anhydrous magnesium sulfate, and filtering is concentrated to give cyclization product.
(4) ring-opening reaction
30g cyclizations product and 100g ethanol are added in there-necked flask, 30% methylethylolamine solution 47g are added dropwise at room temperature,
Drip follow-up continuous insulation reaction 16 hours, reaction is filtered after terminating, gained tide product directly obtain open-loop products with ethyl alcohol recrystallization.
(5) synthesis of ranitidine
Added in there-necked flask 100g water, 30g open-loop products, 30g2- [(dimethylamino) methyl] -5 Chloromethyl-furans and
12.3g potassium hydroxide, then heats to 45 DEG C, and insulation reaction 2 hours is concentrated under reduced pressure dry at 50~60 DEG C by water after having reacted,
50g ethanol is subsequently adding, 40~50 DEG C are heated to, filtering, filtrate is cooled to -5~0 DEG C of insulation and crystallizes 4 hours, and filtering is dried
Obtain ranitidine.
Claims (9)
1. it is a kind of synthesize ranitidine method, it is characterised in that comprise the following steps：
（1）Synthesis vinylidene chloride：
With 1,1,2- trichloroethanes is raw material, sodium hydrate aqueous solution reaction is added dropwise under the conditions of 30~35 DEG C and obtains inclined two chloroethene
Alkene；The 1,1,2- trichloroethanes is 1 with the mass ratio of NaOH:0.3~0.33；
（2）The synthesis of the chloro- 2- nitroethylenes of 1,1- bis-：
By concentrated hydrochloric acid and concentrated nitric acid with mass ratio 1:1~1.2 is mixed into mixed acid；Dripped at 20~25 DEG C to the mixed acid
Plus step（1）The vinylidene chloride for obtaining, after reacting 2~4 hours, is extracted with chloroform or dichloromethane after adding water, washed, done
It is dry, filter, be concentrated to give the chloro- 2- nitroethylenes of 1,1- bis-；The vinylidene chloride is 1 with the mass ratio of mixed acid:2~3；
（3）Ring closure reaction：
In NaOH or potassium hydroxide aqueous solution, Mercaptamine is added, step is added dropwise at 50~55 DEG C（2）Obtain
The chloro- 2- nitroethylenes of 1,1- bis-, reaction extracts with chloroform or dichloromethane, dries, filters, being concentrated to give pass after 1~2 hour
Ring product；Described NaOH or potassium hydroxide and the mol ratio of the chloro- 2- nitroethylenes of 1,1- bis- are 4 ~ 4.5:1；
（4）Ring-opening reaction
By step（3）Gained cyclization product reacts 14~18 hours at room temperature with methylamine in ethanol or methyl alcohol, filters, ties again
Crystalline substance obtains open-loop products；The cyclization product is 1 with the mol ratio of methylamine:2~2.2；
（5）The synthesis of ranitidine
By step（4）Gained open-loop products add potassium hydroxide or hydrogen-oxygen with 2- [(dimethylamino) methyl] -5 Chloromethyl-furans
Change sodium water solution, in 40 ~ 50 DEG C, reaction is concentrated under reduced pressure after 2~4 hours, recrystallizes, filters, cools down, crystallizes, is dried to obtain thunder
Buddhist nun replaces fourth；Described potassium hydroxide or NaOH and the mol ratio of open-loop products are 1.1 ~ 1.3:1.
2. method according to claim 1, it is characterised in that step（1）Described naoh concentration is preferably hydrogen-oxygen
Change sodium mass fraction 30%.
3. method according to claim 1, it is characterised in that step（1）Described 1,1,2- trichloroethanes and hydroxide
The amount ratio of sodium is preferably 1:0.3.
4. method according to claim 1, it is characterised in that step（2）And step（3）Described extraction preferably uses chlorine
Imitative extraction.
5. method according to claim 1, it is characterised in that step（2）Described washing be with 5% sodium acid carbonate it is molten
Liquid is washed；Described drying is to be dried with anhydrous magnesium sulfate.
6. method according to claim 1, it is characterised in that step（2）Described vinylidene chloride and the matter of mixed acid
Amount ratio preferably 1:2.5；Step（3）The mol ratio of described NaOH or potassium hydroxide and the chloro- 2- nitroethylenes of 1,1- bis-
Preferably 4.2:1；Step（4）Described cyclization product is preferably 1 with the mol ratio of methylamine:2.1；Step（5）Described hydrogen-oxygen
Change potassium or NaOH and be preferably 1.2 with the mol ratio of open-loop products:1.
7. method according to claim 1, it is characterised in that step（3）The drying is to be dried with anhydrous magnesium sulfate.
8. method according to claim 1, it is characterised in that step（4）Described recrystallization is to use ethyl alcohol recrystallization.
9. according to any described method of claim 1~7, it is characterised in that comprise the following steps：
（1）Synthesis vinylidene chloride：
With 1,1,2- trichloroethanes is raw material, the reaction of 30% sodium hydrate aqueous solution is added dropwise under the conditions of 30 ~ 35 DEG C and obtains inclined dichloro
Ethene；The 1,1,2- trichloroethanes is 1 with the mass ratio of NaOH: 1.1；
（2）The synthesis of the chloro- 2- nitroethylenes of 1,1- bis-：
By concentrated hydrochloric acid and concentrated nitric acid with mass ratio 1:1 is mixed into mixed acid；In step is added dropwise at 20~25 DEG C（1）To the mixing
After the vinylidene chloride obtained in acid, reaction 3 hours, extracted with chloroform or dichloromethane after adding water, washing, dry, it is filtering, dense
Contracting obtains the chloro- 2- nitroethylenes of 1,1- bis-；The vinylidene chloride is 1 with the mass ratio of mixed acid:2~3；
（3）Ring closure reaction：
In sodium hydrate aqueous solution, Mercaptamine is added, step is added dropwise at 50~55 DEG C（2）The 1,1- bis- for obtaining
Chloro- 2- nitroethylenes, reaction is extracted with chloroform or dichloromethane after 1 hour, dries, filters, being concentrated to give cyclization product；It is described
NaOH or the mol ratio of potassium hydroxide and the chloro- 2- nitroethylenes of 1,1- bis- be 4 ~ 4.5:1；
（4）Ring-opening reaction
By step（3）Gained cyclization product reacts 16 hours at room temperature with methylamine in ethanol or methyl alcohol, filters, recrystallizes
To open-loop products；Cyclization product is 1 with the mole ratio of methylamine:2~1:2.2；
（5）The synthesis of ranitidine
By step（4）Gained open-loop products add potassium hydroxide aqueous solution with 2- [(dimethylamino) methyl] -5 Chloromethyl-furans,
In 40 ~ 50 DEG C, reaction is concentrated under reduced pressure after 2 hours, recrystallizes, filters, cools down, crystallizes, is dried to obtain ranitidine；Described hydrogen
Potassium oxide is 1.1 ~ 1.3 with the mol ratio of open-loop products:1.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108864001A (en) * | 2018-06-30 | 2018-11-23 | 郑州明泽医药科技有限公司 | A kind of new method synthesizing ranitidine |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0115323A2 (en) * | 1983-01-28 | 1984-08-08 | Ube Industries, Ltd. | Process for producing heterocyclic compound having nitromethylene group as the side chain group |
| CN1168669A (en) * | 1994-12-08 | 1997-12-24 | 赫彻斯特马里恩鲁斯公司 | Novel processes for preparing ranitidine |
-
2017
- 2017-04-21 CN CN201710267791.8A patent/CN106892885A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0115323A2 (en) * | 1983-01-28 | 1984-08-08 | Ube Industries, Ltd. | Process for producing heterocyclic compound having nitromethylene group as the side chain group |
| CN1168669A (en) * | 1994-12-08 | 1997-12-24 | 赫彻斯特马里恩鲁斯公司 | Novel processes for preparing ranitidine |
Non-Patent Citations (2)
| Title |
|---|
| 贾正桂等: "1,1-二氯-2-硝基乙烯的合成", 《精细化工中间体》 * |
| 韩祖凤等: "雷尼替丁合成路线概述", 《医药工业》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108864001A (en) * | 2018-06-30 | 2018-11-23 | 郑州明泽医药科技有限公司 | A kind of new method synthesizing ranitidine |
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