CN104447620A - Preparation method of 1-[3-[3-(4-chlorphenyl) propoxy] propyl]-piperidine hydrochloride - Google Patents
Preparation method of 1-[3-[3-(4-chlorphenyl) propoxy] propyl]-piperidine hydrochloride Download PDFInfo
- Publication number
- CN104447620A CN104447620A CN201410715251.8A CN201410715251A CN104447620A CN 104447620 A CN104447620 A CN 104447620A CN 201410715251 A CN201410715251 A CN 201410715251A CN 104447620 A CN104447620 A CN 104447620A
- Authority
- CN
- China
- Prior art keywords
- preparation
- propoxy
- piperidines
- propyl
- chloro
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
Abstract
The invention relates to a preparation method of 1-[3-[3-(4-chlorphenyl) propoxy] propyl]-piperidine hydrochloride. The preparation method of 1-[3-[3-(4-chlorphenyl) propoxy] propyl]-piperidine hydrochloride comprises the following steps: (1) putting piperidine and 1,3-dihalogen propane in a water-soluble polar aprotic solvent, and carrying out condensation reaction to obtain N-(3-halide propyl) piperidine under the action of an alkali compound; (2) carrying out etherification on N-(3-halide propyl) piperidine and 3-(4-chlorphenyl) propyl alcohol in the solvent under the action of the alkali compound to obtain a compound, namely 1-[3-[3-(4-chlorphenyl) propoxy] propyl]-piperidine; and (3) enabling the 1-[3-[3-(4-chlorphenyl) propoxy] propyl]-piperidine to react with HCl to obtain the product. The preparation method of 1-[3-[3-(4-chlorphenyl) propoxy] propyl]-piperidine hydrochloride is simple in processing step, convenient to operate, easily available in raw material and low in price; the prepared product is high in yield, high in purity, low in cost and suitable for industrial production.
Description
Technical field
The present invention relates to a kind of 1 ?[3 ?[3 ?(4 ?chloro-phenyl-) propoxy-] propyl group] ?the preparation method of piperidine hydrochlorate, belong to technical field of medicine synthesis.
Background technology
1 ?[3 ?[3 ?(4 ?chloro-phenyl-) propoxy-] propyl group] ?piperidine hydrochlorate, formula (I), also referred to as replacing Luo Lisheng (tiprolisant), be by Bioprojet ?Biotech company develop receptor antagonist, it shows the stronger avidity of histamine H 3 receptor and selectivity.Carrying out the three phases clinical study of transitional sleep in the daytime (EDS) symptom being used for the treatment of the various diseases such as lethargy, parkinsonism at present.It has the features such as oral, potent, side effect is little, and potential applicability in clinical practice is optimistic.
Patent WO2007/006708 adopts 1 ?piperidinepropanol and 3 ?(4 ?chloro-phenyl-) propyl Methanesulfonate to prepare for Luo Lisheng, expensive raw material price, and is not easy to obtain, and cost is higher.Patent CN101155793 reacts with 3 ?(1 ?piperidines) sodium propylate and 3 ?(4 ?chloro-phenyl-) propyl Methanesulfonate and prepares for Luo Lisheng, expensive raw material price, and be not easy to obtain, cost is higher, used the large catalyzer of toxicity 15 ?Guan ?5, the fractionation operation of column chromatography and more than 200 DEG C has been used in aftertreatment, is unfavorable for suitability for industrialized production.Patent CN103435575 with 3 ?(4 ?chloro-phenyl-) propionic acid for raw material, through reduction, esterification obtain 3 ?(4 ?chloro-phenyl-) propyl Methanesulfonate, take piperidines as raw material, through N ?alkylation obtain 1 ?piperidinepropanol, after 3 ?(4 ?chloro-phenyl-) propyl Methanesulfonate and 1 ?piperidinepropanol react, salify obtains for Luo Lisheng, the method step is oversize, complicated operation, and cost is high.All Luo Lisheng is replaced by the synthesis of 3-(4-chloro-phenyl-) propyl Methanesulfonate in prior art, methanesulfonates compounds is genotoxicity impurity or potential genotoxicity impurity, in medicine, genotoxicity limit of impurities needs strict control, improves technique controlling difficulty.
Summary of the invention
The invention provides the preparation method of a kind of 1-[3-[3-(4-chloro-phenyl-) propoxy-] propyl group]-piperidine hydrochlorate, avoid replacing Luo Lisheng by methanesulfonates compounds as intermediate synthesis, present invention process step is simple, easy to operate, raw material is easy to get, low price, and the product yield of preparation is high, purity is high, and cost is low.
Of the present invention 1 ?[3 ?[3 ?(4 ?chloro-phenyl-) propoxy-] propyl group] ?the preparation method of piperidine hydrochlorate, comprise the following steps:
(1) by piperidines and 1,3 ?dihalopropane be placed in water miscible polar aprotic solvent, under basic cpd effect, condensation reaction obtain N ?(3 ?halogen propyl group) piperidines;
(2) N ?(3 ?halogen propyl group) piperidines and 3 ?(4 ?chloro-phenyl-) propyl alcohol in a solvent, carry out etherificate under basic cpd effect, obtain compound 1 ?[3 ?[3 ?(4 ?chloro-phenyl-) propoxy-] propyl group] ?piperidines;
(3) 1 ?[3 ?[3 ?4 ?chloro-phenyl-) propoxy-] and propyl group] ?piperidines and HCl be obtained by reacting 1 ?[3 ?[3 ?(4 ?chloro-phenyl-) propoxy-] propyl group] ?piperidine hydrochlorate.
In described step (1) 1,3 ?1 halogen in dihalopropane be fluorine, chlorine, bromine or iodine, 3 halogens are fluorine, chlorine, bromine or iodine.
Described step (1) adopts a kind of metal iodide to come as reaction promotor.
Described metal iodide is potassiumiodide or sodium iodide.
In described step (1) water miscible polar aprotic solvent be acetone, methyl ethyl ketone, tetrahydrofuran (THF), methane amide, N, N ?dimethyl formamide or N, N ?in N,N-DIMETHYLACETAMIDE any one or multiple.
Piperidines and 1 in described step (1), 3 ?the mol ratio of dihalopropane formula be 1:1 ?6.Piperidines and 1 in preferred steps (1), 3 ?the mol ratio of dihalopropane formula (II) be 1:1 ?1.5.
In described step (1) temperature of reaction be 20 ?150 DEG C, condensation reaction time be 3h ?30h; In described step (2) temperature of reaction be 20 ?150 DEG C, the etherification reaction time be 3h ?30h.Preferably, in step (1) temperature of reaction be 20 ?100 DEG C, condensation reaction 3h ?30h; In preferred steps (2) temperature of reaction be 20 ?100 DEG C, etherification reaction 3h ?30h.
Described step (2) described solvent for for lower alcohol, ketone, ether, aromatic hydrocarbons, acetonitrile, any one or mixing two or more arbitrarily in DMF, DMA, DMSO or hexamethyl phosphoric triamide.
Lower alcohol is methyl alcohol, ethanol or Virahol, and ketone is acetone or methylethylketone, and ether Wei diox or diglyme, aromatic hydrocarbons is toluene or dimethylbenzene.
In described step (2), N ?(3 ?halogen propyl group) piperidines formula and 3 ?the mol ratio of (4 ?chloro-phenyl-) propyl alcohol formula be 0.5 ?2:1.Preferred steps (2) described N ?(3 ?halogen propyl group) piperidines formula and 3 ?(4 ?chloro-phenyl-) propyl alcohol formula mole be 0.7 ?1.5:1.
Basic cpd in described step (1) and (2) is inorganic alkaline compound, alkali metal alcoholate or organic basic compound.Basic cpd is as a kind of dehydrohalogenation reagent.
Described inorganic alkaline compound is potassium hydroxide, sodium hydroxide, sodium carbonate, salt of wormwood, sodium hydride, potassium metal or sodium amide, described alkali metal alcoholate is sodium methylate, sodium ethylate or potassium ethylate, and organic basic compound is tertiary amine, pyridine, quinoline, triethylamine or tripropylamine.
Reaction equation of the present invention is as follows:
1 ?[3 ?[3 ?(4 ?chloro-phenyl-) propoxy-] propyl group] the ?piperidine hydrochlorate that above-mentioned preparation method obtains, 1 ?[3 ?[3 ?(4 ?chloro-phenyl-) propoxy-] propyl group] ?piperidine hydrochlorate is for Luo Lisheng.
Compared with prior art, the present invention has following beneficial effect:
The present invention avoids replacing Luo Lisheng by methanesulfonates compounds as intermediate synthesis, and present invention process step is simple, and easy to operate, raw material is easy to get, and low price is simple, and the product yield of preparation is high, and purity is high, and cost is low, is applicable to suitability for industrialized production.
Embodiment
Be described further the present invention below in conjunction with embodiment, the following example only for illustration of the present invention, and should not be considered as limiting scope of the present invention.Unreceipted actual conditions person in embodiment, the condition of conveniently conditioned disjunction manufacturers suggestion is carried out.Agents useful for same or the unreceipted manufacturer person of instrument, being can by the product of commercial acquisition.
Embodiment 1
N ?the synthesis of (3 ?bromopropyl) piperidines
By tetrahydrofuran (THF) (200ml), piperidines (17.2g, 0.2mol), 1,3 ?dibromopropane (60.6g, 0.3mol), sodium carbonate (11.1g, 0.105mol) add reaction flask successively, 67 DEG C of back flow reaction 12 hours.Be cooled to room temperature, filter, filtrate concentrates, residue 2N dissolving with hydrochloric acid, and ethyl acetate washs 2 times, and aqueous phase 2N NaOH solution adjusts pH to 10, is extracted with ethyl acetate 3 times, merges organic phase, anhydrous magnesium sulfate drying.Filter, concentrating under reduced pressure obtains pale yellow oil 39.1g, yield 94.9%.
1 ?[3 ?[3 ?(4 ?chloro-phenyl-) propoxy-] propyl group] ?piperidine hydrochlorate
By 3 ?(4 ?chloro-phenyl-) propyl alcohol (17.1g, 0.1mol) join in DMF (170ml), NaH (the 3g of 60% is slowly added at 0 DEG C, 0.1mol), stir 30 minutes, then add N ?(3 ?bromopropyl) piperidines (22.6g, 0.11mol) solution in DMF (30mL).Mixture is stirred 2 hours at 0 DEG C, then 20 DEG C of reactions 8 hours.Then dilute with the water of 400ml, by ethyl acetate 400ml extracting twice, merge organic phase, wash twice with 2N sodium hydroxide and salt solution, by dried over mgso, filter, under room temperature, pass into HCl gas, stir and separate out solid, filter, drying, obtains obtaining faint yellow solid product 30.7g, yield 92.5%.
The HPLC:99.7% of product.mp：117～120℃。
1H‐NMR(400MHz，D
2O)δ：1.20～1.31(1H,br),1.42～1.57(2H,br),1.58～1.80(7H,br),2.44(2H,t),2.65(2H,t),2.86(2H,t),3.22～3.36(6H,br),7.02(2H,d),7.12(2H,d)。MS m/z：296[M‐HCl]。IR(KBr)：2936cm
‐1，2868cm
‐1，2647cm
‐1，2551cm
‐1，1492cm
‐1，1455cm
‐1，1112cm
‐1，1101cm
‐1，802cm
‐1。
Embodiment 2
N ?the synthesis of (3 ?bromopropyl) piperidines
By DMF (200ml), piperidines (17.2g, 0.2mol), 1,3 ?dibromopropane (60.6g, 0.3mol), salt of wormwood (14.5g, 0.105mol) sodium iodide (4.5g, 0.03mol) add reaction flask successively, 150 DEG C are reacted 4 hours.Be cooled to room temperature, filter, filtrate concentrates, residue 2N dissolving with hydrochloric acid, and ethyl acetate washs 2 times, and aqueous phase 2N NaOH solution adjusts pH to 10, is extracted with ethyl acetate 3 times, merges organic phase, anhydrous magnesium sulfate drying.Filter, concentrating under reduced pressure obtains pale yellow oil 37.2g, yield 90.4%.
1 ?[3 ?[3 ?(4 ?chloro-phenyl-) propoxy-] propyl group] ?piperidine hydrochlorate
By 3 ?(4 ?chloro-phenyl-) propyl alcohol (17.1g, 0.1mol) join in DMA (170ml), NaOH (the 3g of 60% is slowly added at 0 DEG C, 0.1mol), stir 30 minutes, then add N ?(3 ?bromopropyl) piperidines (22.6g, 0.11mol) solution in DMA (30mL).Mixture is stirred 2 hours at 0 DEG C, is then warming up to 150 DEG C of reactions 4 hours.Mixture is cooled to room temperature, then dilutes with the water of 400ml, by ethyl acetate 400ml extracting twice, merge organic phase, wash twice with 2N sodium hydroxide and salt solution, by dried over mgso, filter, pass into HCl gas under room temperature, stir and separate out solid, filter, dry, obtain obtaining faint yellow solid 29.6g, yield 89.2%, HPLC:99.5%.
Embodiment 3
N ?the synthesis of (3 ?bromopropyl) piperidines
By acetone (200ml), piperidines (17.2g, 0.2mol), 1,3 ?dibromopropane (60.6g, 0.3mol), salt of wormwood (14.5g, 0.105mol) potassiumiodide (5g, 0.03mol) add reaction flask successively, 56 DEG C of back flow reaction 10 hours.Be cooled to room temperature, filter, filtrate concentrates, residue 2N dissolving with hydrochloric acid, and ethyl acetate washs 2 times, and aqueous phase 2N NaOH solution adjusts pH to 10, is extracted with ethyl acetate 3 times, merges organic phase, anhydrous magnesium sulfate drying.Filter, concentrating under reduced pressure obtains pale yellow oil 37.9g, yield 92.1%.
1 ?[3 ?[3 ?(4 ?chloro-phenyl-) propoxy-] propyl group] ?piperidine hydrochlorate
By 3 ?(4 ?chloro-phenyl-) propyl alcohol (17.1g, 0.1mol) join in tetrahydrofuran (THF) (170ml), NaH (the 3g of 60% is slowly added at 0 DEG C, 0.1mol), stir 30 minutes, then add N ?(3 ?bromopropyl) piperidines (22.6g, 0.11mol) solution in DMA (30mL).Mixture is stirred 2 hours at 0 DEG C, then 25 DEG C of reactions 10 hours.Then dilute with the water of 400ml, by ethyl acetate 400ml extracting twice, merge organic phase, wash twice with 2N sodium hydroxide and salt solution, by dried over mgso, filter, under room temperature, pass into HCl gas, stir and separate out solid, filter, dry, obtain obtaining faint yellow solid 30.0g, yield 90.4%, HPLC:99.6%.
Embodiment 4
N ?the synthesis of (3 ?chloropropyl) piperidines
By acetone (200ml), piperidines (17.2g, 0.2mol), 1,3 ?bromo-chloropropane (47.2g, 0.3mol), sodium carbonate (11.1g, 0.105mol) add reaction flask successively, 20 DEG C of reactions 30 hours.Filter, filtrate concentrates, residue 2N dissolving with hydrochloric acid, and ethyl acetate washs 2 times, and aqueous phase 2N NaOH solution adjusts pH to 10, is extracted with ethyl acetate 3 times, merges organic phase, anhydrous magnesium sulfate drying.Filter, concentrating under reduced pressure obtains pale yellow oil 28.6g, yield 88.3%.
1 ?[3 ?[3 ?(4 ?chloro-phenyl-) propoxy-] propyl group] ?piperidine hydrochlorate
By 3 ?(4 ?chloro-phenyl-) propyl alcohol (17.1g, 0.1mol) join in DMF (170ml), NaH (the 3g of 60% is slowly added at 0 DEG C, 0.1mol), stir 30 minutes, then add N ?(3 ?bromopropyl) piperidines (22.6g, 0.11mol) solution in DMA (30mL).Mixture is stirred 2 hours at 0 DEG C, then reacts 8 hours at 20 DEG C.Then dilute with the water of 400ml, by ethyl acetate 400ml extracting twice, merge organic phase, wash twice with 2N sodium hydroxide and salt solution, by dried over mgso, filter, under room temperature, pass into HCl gas, stir and separate out solid, filter, dry, obtain obtaining faint yellow solid 30.4g, yield 91.7%, HPLC:99.6%.
Embodiment 5
N ?the synthesis of (3 ?chloropropyl) piperidines
By DMF (200ml), piperidines (17.2g, 0.2mol), 1,3 ?bromo-chloropropane (47.2g, 0.3mol), sodium carbonate (11.1g, 0.105mol), sodium iodide 1g adds reaction flask successively, 150 DEG C of back flow reaction 3 hours.Be cooled to room temperature, filter, filtrate concentrates, residue 2N dissolving with hydrochloric acid, and ethyl acetate washs 2 times, and aqueous phase 2N NaOH solution adjusts pH to 10, is extracted with ethyl acetate 3 times, merges organic phase, anhydrous magnesium sulfate drying.Filter, concentrating under reduced pressure obtains pale yellow oil 28.8g, yield 89.1%.
1 ?[3 ?[3 ?(4 ?chloro-phenyl-) propoxy-] propyl group] ?piperidine hydrochlorate
By 3 ?(4 ?chloro-phenyl-) propyl alcohol (17.1g, 0.1mol) join in DMA (170ml), NaH (the 3g of 60% is slowly added at 0 DEG C, 0.1mol), stir 30 minutes, then add N ?(3 ?bromopropyl) piperidines (22.6g, 0.11mol) solution in DMA (30mL).Mixture is stirred 2 hours at 0 DEG C, then 20 DEG C of reactions 8 hours.Then dilute with the water of 400ml, by ethyl acetate 400ml extracting twice, merge organic phase, wash twice with 2N sodium hydroxide and salt solution, by dried over mgso, filter, under room temperature, pass into HCl gas, stir and separate out solid, filter, dry, obtain obtaining faint yellow solid 29.7g, yield 89.6%, HPLC:99.7%.
Embodiment 6
N ?the synthesis of (3 ?chloropropyl) piperidines
By tetrahydrofuran (THF) (200ml), piperidines (17.2g, 0.2mol), 1,3 ?bromo-chloropropane (47.2g, 0.3mol), sodium carbonate (11.1g, 0.105mol) add reaction flask successively, 66 DEG C of back flow reaction 15 hours.Be cooled to room temperature, filter, filtrate concentrates, residue 2N dissolving with hydrochloric acid, and ethyl acetate washs 2 times, and aqueous phase 2N NaOH solution adjusts pH to 10, is extracted with ethyl acetate 3 times, merges organic phase, anhydrous magnesium sulfate drying.Filter, concentrating under reduced pressure obtains pale yellow oil 30.2g, yield 93.4%.
1 ?[3 ?[3 ?(4 ?chloro-phenyl-) propoxy-] propyl group] ?piperidine hydrochlorate
By 3 ?(4 ?chloro-phenyl-) propyl alcohol (17.1g, 0.1mol) join in DMF (150ml), add successively N ?(3 ?chloropropyl) piperidines (17.8g, 0.11mol), salt of wormwood (6.9g, 0.05mol), potassiumiodide 1g, be heated to 95 DEG C, stirring reaction 12 hours.Mixture is cooled to room temperature, then dilutes with the water of 300ml, by ethyl acetate 400ml extracting twice, merge organic phase, wash twice with 2N sodium hydroxide and salt solution, by dried over mgso, filter, pass into HCl gas under room temperature, stir and separate out solid, filter, dry, obtain obtaining faint yellow solid 29.8g, yield 89.7%, HPLC:99.6%.
Claims (10)
1. a preparation method for 1-[3-[3-(4-chloro-phenyl-) propoxy-] propyl group]-piperidine hydrochlorate, is characterized in that, comprise the following steps:
(1) piperidines and 1,3-dihalopropane are placed in water miscible polar aprotic solvent, under basic cpd effect, condensation reaction obtains N-(3-halogen propyl group) piperidines;
(2) N-(3-halogen propyl group) piperidines and 3-(4-chloro-phenyl-) propyl alcohol in a solvent, carry out etherificate under basic cpd effect, obtain compound 1-[3-[3-(4-chloro-phenyl-) propoxy-] propyl group]-piperidines;
(3) 1-[3-[3-4-chloro-phenyl-) propoxy-] propyl group]-piperidines and HCl be obtained by reacting 1-[3-[3-(4-chloro-phenyl-) propoxy-] propyl group]-piperidine hydrochlorate.
2. preparation method according to claim 1, is characterized in that, 1 halogen in 1,3-dihalopropane in described step (1) is fluorine, chlorine, bromine or iodine, and 3 halogens are fluorine, chlorine, bromine or iodine.
3. preparation method according to claim 1, is characterized in that, described step (1) adopts a kind of metal iodide to come as reaction promotor.
4. preparation method according to claim 3, is characterized in that, described metal iodide is potassiumiodide or sodium iodide.
5. preparation method according to claim 1, it is characterized in that, in described step (1), water miscible polar aprotic solvent is acetone, methyl ethyl ketone, tetrahydrofuran (THF), methane amide, N, in dinethylformamide or N,N-dimethylacetamide any one or multiple.
6. preparation method according to claim 1, is characterized in that, in described step (1), the mol ratio of piperidines and 1,3-dihalopropane formula is 1:1-6.
7. preparation method according to claim 1, is characterized in that, in described step (1), temperature of reaction is 20-150 DEG C, and condensation reaction time is 3h-30h; In described step (2), temperature of reaction is 20-150 DEG C, and the etherification reaction time is 3h-30h.
8. preparation method according to claim 1, it is characterized in that, described step (2) described solvent is for being lower alcohol, ketone, ether, aromatic hydrocarbons, acetonitrile, DMF, any one or mixing two or more arbitrarily in DMA, DMSO or hexamethyl phosphoric triamide.
9. preparation method according to claim 1, is characterized in that, in described step (2), the mol ratio of N-(3-halogen propyl group) piperidines formula and 3-(4-chloro-phenyl-) propyl alcohol formula is 0.5-2:1.
10. preparation method according to claim 1, is characterized in that, the basic cpd in described step (1) and (2) is inorganic alkaline compound, alkali metal alcoholate or organic basic compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410715251.8A CN104447620B (en) | 2014-11-28 | 2014-11-28 | 1-[3-[3-(4-chlorphenyl) propoxyl group] propyl group] preparation method of-piperidine hydrochlorate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410715251.8A CN104447620B (en) | 2014-11-28 | 2014-11-28 | 1-[3-[3-(4-chlorphenyl) propoxyl group] propyl group] preparation method of-piperidine hydrochlorate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104447620A true CN104447620A (en) | 2015-03-25 |
| CN104447620B CN104447620B (en) | 2016-05-04 |
Family
ID=52894446
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410715251.8A Active CN104447620B (en) | 2014-11-28 | 2014-11-28 | 1-[3-[3-(4-chlorphenyl) propoxyl group] propyl group] preparation method of-piperidine hydrochlorate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104447620B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106749101A (en) * | 2016-12-30 | 2017-05-31 | 湖南千金湘江药业股份有限公司 | A kind of preparation method of difenidol hydrochloride |
| CN108467372A (en) * | 2018-04-26 | 2018-08-31 | 江苏四环生物制药有限公司 | The preparation method of difenidol hydrochloride |
| CN110804026A (en) * | 2019-11-18 | 2020-02-18 | 苏州永健生物医药有限公司 | Synthesis method of 1- (3- (3- (4-chlorphenyl) propoxy) propyl) piperidine hydrochloride |
| IT201900013941A1 (en) | 2019-08-05 | 2021-02-05 | Procos Spa | PROCESS FOR THE SYNTHESIS OF PITOLISANT HCl |
| CN116640104A (en) * | 2023-05-24 | 2023-08-25 | 杭州科耀医药科技有限公司 | Industrial synthesis method of telithromycin |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007006708A1 (en) * | 2005-07-08 | 2007-01-18 | Bioprojet | Process for preparing 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-piperidine |
| CN101155793A (en) * | 2005-02-10 | 2008-04-02 | 生物计划公司 | Monohydrochloride salt of 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-piperidine |
| CN103435575A (en) * | 2013-08-06 | 2013-12-11 | 中国人民解放军军事医学科学院毒物药物研究所 | Preparation method of 1-(3-(3-(4-chlorphenyl) propoxy) propyl) piperidine hydrochloride |
-
2014
- 2014-11-28 CN CN201410715251.8A patent/CN104447620B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101155793A (en) * | 2005-02-10 | 2008-04-02 | 生物计划公司 | Monohydrochloride salt of 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-piperidine |
| WO2007006708A1 (en) * | 2005-07-08 | 2007-01-18 | Bioprojet | Process for preparing 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-piperidine |
| CN103435575A (en) * | 2013-08-06 | 2013-12-11 | 中国人民解放军军事医学科学院毒物药物研究所 | Preparation method of 1-(3-(3-(4-chlorphenyl) propoxy) propyl) piperidine hydrochloride |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106749101A (en) * | 2016-12-30 | 2017-05-31 | 湖南千金湘江药业股份有限公司 | A kind of preparation method of difenidol hydrochloride |
| CN106749101B (en) * | 2016-12-30 | 2019-07-12 | 湖南千金湘江药业股份有限公司 | A kind of preparation method of difenidol hydrochloride |
| CN108467372A (en) * | 2018-04-26 | 2018-08-31 | 江苏四环生物制药有限公司 | The preparation method of difenidol hydrochloride |
| IT201900013941A1 (en) | 2019-08-05 | 2021-02-05 | Procos Spa | PROCESS FOR THE SYNTHESIS OF PITOLISANT HCl |
| WO2021023634A1 (en) | 2019-08-05 | 2021-02-11 | Procos S.P.A. | PROCESS FOR THE SYNTHESIS OF PITOLISANT HCl |
| CN110804026A (en) * | 2019-11-18 | 2020-02-18 | 苏州永健生物医药有限公司 | Synthesis method of 1- (3- (3- (4-chlorphenyl) propoxy) propyl) piperidine hydrochloride |
| CN110804026B (en) * | 2019-11-18 | 2022-04-01 | 苏州永健生物医药有限公司 | Synthesis method of 1- (3- (3- (4-chlorphenyl) propoxy) propyl) piperidine hydrochloride |
| CN116640104A (en) * | 2023-05-24 | 2023-08-25 | 杭州科耀医药科技有限公司 | Industrial synthesis method of telithromycin |
| CN116640104B (en) * | 2023-05-24 | 2024-04-02 | 杭州科耀医药科技有限公司 | Industrial synthesis method of telithromycin |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104447620B (en) | 2016-05-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104447620A (en) | Preparation method of 1-[3-[3-(4-chlorphenyl) propoxy] propyl]-piperidine hydrochloride | |
| CN110526859B (en) | Revinanexin intermediate, preparation method thereof and preparation method of Revinanexin | |
| KR101420892B1 (en) | Process for the preparation of Imatinib and intermediates thereof | |
| CN104926775A (en) | Preparation method of fluorine-containing pyran derivative | |
| CN106543060A (en) | It is a kind of it is difficult to understand this for Buddhist nun's mesylate preparation method | |
| CN103435575A (en) | Preparation method of 1-(3-(3-(4-chlorphenyl) propoxy) propyl) piperidine hydrochloride | |
| CN104045606B (en) | One kettle way prepares the method for Ah examining for amine hydrochlorate | |
| CN102020634B (en) | Preparation method of N-(w-cyanoalkyl) benzamide compounds | |
| CN103601645A (en) | Preparation method of 1-(phenethylamino) propane-2-alcoholic compounds or salts thereof | |
| CN116829554A (en) | Intermediate for thiohydantoin drug and preparation method and application thereof | |
| CN102796090B (en) | Method for preparing iloperidone | |
| CN108947919B (en) | Novel preparation method of anti-gout drug Lesinurad and key intermediate thereof | |
| CN105017066A (en) | Chlorinated azide preparation method | |
| CN105753735B (en) | Preparation method of high-efficiency low-toxicity vasopressin antagonist | |
| JP2015038053A (en) | Method for producing 4-(2-methyl-1-imidazolyl)-2,2-phenylbutane amide | |
| CN104292213A (en) | Preparation method of pyrimidine derivative | |
| CN102731474B (en) | Preparation method of imatinib | |
| CN106349214B (en) | Preparation method of bilastine impurity | |
| CN105884746A (en) | Synthesizing method of flumatinib | |
| CN101863836B (en) | Method for preparing 5,5-diphenyl-2-thiohydantoin | |
| CN105061253A (en) | Preparation method of bromine-containing azide | |
| CN105061254A (en) | Synthetic method of bromine-containing azide | |
| CN103755657A (en) | Preparation method of rivaroxaban intermediate | |
| CN104163798A (en) | Synthesis method of 3-amino-8-trifluoromethyl quinoline | |
| CN110218211B (en) | Simple preparation method of nevirapine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 256100 No. 6 Erlang Road, Yiyuan County, Zibo, Shandong Patentee after: Ruiyang Pharmaceutical Co., Ltd Address before: 256100 No. 6 Erlang Road, Yiyuan County, Zibo, Shandong Patentee before: REYOUNG PHARMACEUTICAL Co.,Ltd. |
|
| CP01 | Change in the name or title of a patent holder |