CN104926665A - Method for synthesizing cinacalcet - Google Patents
Method for synthesizing cinacalcet Download PDFInfo
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- CN104926665A CN104926665A CN201510181537.7A CN201510181537A CN104926665A CN 104926665 A CN104926665 A CN 104926665A CN 201510181537 A CN201510181537 A CN 201510181537A CN 104926665 A CN104926665 A CN 104926665A
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- naphthyl
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- VDHAWDNDOKGFTD-UHFFFAOYSA-N CC(c1cccc2ccccc12)NCCCc1cccc(C(F)(F)F)c1 Chemical compound CC(c1cccc2ccccc12)NCCCc1cccc(C(F)(F)F)c1 VDHAWDNDOKGFTD-UHFFFAOYSA-N 0.000 description 1
- GDEHAOJGPHEOSO-OAHLLOKOSA-N C[C@H](c1c(cccc2)c2ccc1)NC(CCc1cccc(C(F)(F)F)c1)=O Chemical compound C[C@H](c1c(cccc2)c2ccc1)NC(CCc1cccc(C(F)(F)F)c1)=O GDEHAOJGPHEOSO-OAHLLOKOSA-N 0.000 description 1
- RTCUCQWIICFPOD-SECBINFHSA-N C[C@H](c1cccc2ccccc12)N Chemical compound C[C@H](c1cccc2ccccc12)N RTCUCQWIICFPOD-SECBINFHSA-N 0.000 description 1
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Abstract
The invention provides a method for synthesizing cinacalcet. According to the method, (R)-1-(1-naphthyl)ethylamine and 3-(3-trifluoromethylphenyl)propionic acid are adopted as raw materials; a nonmetal boron compound is adopted as a catalyst; an organosilane compound is adopted as a reducing agent; and a target product is synthesized with one step through a reductive coupling process. The method provided by the invention is simple and is easy to operate; and the raw materials are easy to obtain, such that cost is low. Also, no metal catalyst is needed in the synthesis process, such that metal residue in the drug is avoided, and the method is safe and environment-friendly. The method meets the requirements of green chemistry.
Description
Technical field
The present invention relates to pharmaceutical chemistry synthesis field, be specifically related to a kind of method of synthesis cinacalcet (Cinacalcet).
Background technology
The chemistry of cinacalcet is called: N-((1R)-1-(1-naphthyl) ethyl)-3-(3-(trifluoromethyl) phenyl) the third-1-amine, and its structure is represented by following formula (III):
Traditional secondary hyperparathyroidism (secondary hyperparathyroidism) treatment means comprises use phosphate binder and supplementary activated cellulose D, but the compliance rate for the treatment of is low.Cinacalcet hydrochloride is first medicine in the new class compound of Sensipar, it is by activating the mode of the calcium acceptor on parathyroid cells, reach the effect directly suppressing Rat parathyroid hormone 1-34 (PTH) to be secreted, and it has the effect for the treatment of primary and secondary hyperparathyroidism.In addition, it is used for the treatment of the Secondary hyperparathyroidism of ephrosis dialysis patients, and has good curative effect to the hypercalcemia (hypercalcinemia) caused by the other cancer of Thyreoidine.Cinacalcet hydrochloride is that cinacalcet is prepared through hcl acidifying salify, is the Sensipar researched and developed by NPS Pharmaceuticals company of the U.S..2004, the cinacalcet hydrochloride listing that U.S. FDA approval Amgen company produces, commodity are called Sensipar; 2007, the cinacalcet hydrochloride that kylin drugmaker produces went on the market in Japan, and commodity are called REGPARA, have now been widely used in clinical.
WO2007127445 disclose directly with 3-[3-(trifluoromethyl) phenyl]-2-vinylformic acid for starting raw material, through reduction, replacement, amidation, the reaction such as to restore, obtain target product cinacalcet (route 1):
For starting raw material, through reactions such as reduction, replacement, condensations, cinacalcet (route 2) is prepared with 3-[3-(trifluoromethyl) phenyl]-2-vinylformic acid in WO2010100429 report:
In the recent period, J.Am.Chem.Soc.2014, in 136 (40): 14314-14319 articles, report directly with (R)-1-(1-naphthyl) ethamine and 3-(3-trifluoromethyl) propionic acid for starting raw material, take noble metal platinum as catalyzer, phenyl silane is reductive agent, realizes single stage method first and prepares cinacalcet (route 3):
But, there is route longer (route 1 described above and route 2) in these methods, complicated operation.In addition, although above-mentioned route 3 achieves one-step synthesis, but yield is lower than 80%, in addition, it needs to use noble metal platinum to participate in catalysis, it is higher that this makes not only to synthesize cost, and due to the participation of metal catalyst, metal can be caused to remain in synthesized medicine, cause obtained medicine to there is unsafe problem, the use of precious metal simultaneously also can make whole building-up process not environmentally, does not meet current Green Chemistry requirement.
Summary of the invention
In order to solve above-mentioned part or all of problem of the prior art, the invention provides a kind of method of novel synthesis cinacalcet.
On the one hand, the present invention relates to a kind of method of synthesizing cinacalcet, described method comprises:
By (R)-1-(1-naphthyl) ethamine of formula (I)
With 3-(3-trifluoromethyl) propionic acid of formula (II)
In organic solvent, take organic silane compound as reductive agent, be that catalyzer issues raw reductive coupling reaction at nonmetal boron compound, and obtain the cinacalcet product of formula (III),
In a preferred embodiment, the ratio of the molar weight of described 3-(3-trifluoromethyl) propionic acid and described (R)-1-(1-naphthyl) ethamine is 1.0-2.5.
In a preferred embodiment, described nonmetal boron compound is at least one in phenylo boric acid, 3,4,5-trifluoro-benzene boric acid, 2,3,4,5-tetra fluoro benzene boric acid, triethyl-boron, three (pentafluorophenyl group) boron.
In a preferred embodiment, described organic silane compound is at least one in triethyl silicane, phenyldimethylsilane, diphenyl silane, diethylsilane, poly-(methyl hydrogen siloxane), phenyl silane.
In a preferred embodiment, described organic solvent is at least one in toluene, m-xylene, sym-trimethylbenzene, diethylene glycol dimethyl ether, Isosorbide-5-Nitrae-dioxane, tetrahydrofuran (THF), n-butyl ether.
In a preferred embodiment, use described nonmetal boron compound be 0.005-0.02 with the ratio of the molar weight of described (R)-1-(1-naphthyl) ethamine.
In a preferred embodiment, the ratio of the described organic silane compound of use and the molar weight of described (R)-1-(1-naphthyl) ethamine is 3.0-5.0.
In a preferred embodiment, the ratio of the volume ml quantity of described organic solvent and the mmole quantity of described (R)-1-(1-naphthyl) ethamine, namely the mole dosage of volume/(R)-1-(1-naphthyl) ethamine of organic solvent, is 2.0-5.0.
In a preferred embodiment, the temperature of described reductive coupling reaction is 80 DEG C-150 DEG C.
In a preferred embodiment, the time of described reductive coupling reaction is 15h-25h.
The present invention by with (R)-1-(1-naphthyl) ethamine and 3-(3-trifluoromethyl) propionic acid for starting raw material, with nonmetal boron compound for catalyzer, use organic silane compound is reductive agent, by the process of reductive coupling, the cinacalcet product that one-step synthesis method is required.Simple synthetic method of the present invention, easy to operate, raw material is easy to get, and cost is lower.Meanwhile, in synthetic method of the present invention, do not use metal-based catalysts, avoid metal remaining in medicine, safety, environmental protection, meets Green Chemistry requirement.
Accompanying drawing explanation
Fig. 1 is the hydrogen nuclear magnetic resonance spectrogram of cinacalcet prepared by the embodiment of the present invention 1;
Fig. 2 is the carbon-13 nmr spectra figure of cinacalcet prepared by the embodiment of the present invention 1;
Fig. 3 is the Enantiomeric excess figure of cinacalcet prepared by the embodiment of the present invention 1.
Embodiment
The present invention by with (R)-1-(1-naphthyl) ethamine and 3-(3-trifluoromethyl) propionic acid for starting raw material, with nonmetal boron compound for catalyzer, use organic silane compound is reductive agent, by the process of reductive coupling, the cinacalcet product that one-step synthesis method is required.
More specifically, the method for synthesis cinacalcet of the present invention comprises: by (R)-1-(1-naphthyl) ethamine of formula (I)
and the 3-of formula (II) (3-trifluoromethyl) propionic acid (I)
(II) in organic solvent, exist at the organic silane compound as reductive agent and the nonmetal boron compound as catalyzer and issue raw reductive coupling reaction, obtain the cinacalcet of formula (III)
(III).
Preferably, 3-(3-trifluoromethyl) propionic acid of use is 1.0-2.5 with the ratio of the molar weight of (R)-1-(1-naphthyl) ethamine, is more preferably 2.0.
Preferably, the nonmetal boron compound of use is phenylo boric acid, 3,4,5-trifluoro-benzene boric acid, 2,3,4,5-tetra fluoro benzene boric acid, triethyl-boron, at least one in three (pentafluorophenyl group) boron, be more preferably three (pentafluorophenyl group) boron.
Preferably, the organic silane compound of use is triethyl silicane, phenyldimethylsilane, diphenyl silane, diethylsilane, poly-(methyl hydrogen siloxane), at least one in phenyl silane, be more preferably phenyl silane.
Preferably, the organic solvent of use is toluene, m-xylene, sym-trimethylbenzene, diethylene glycol dimethyl ether, Isosorbide-5-Nitrae-dioxane, tetrahydrofuran (THF), at least one in n-butyl ether, be more preferably n-butyl ether.
Preferably, the nonmetal boron compound of use is 0.005-0.02 with the ratio of the molar weight of (R)-1-(1-naphthyl) ethamine, is more preferably 0.01.
Preferably, the organic silane compound of use is 3.0-5.0 with the ratio of the molar weight of (R)-1-(1-naphthyl) ethamine, is more preferably 4.0.
Preferably, the volume (ml quantity) of organic solvent used and the ratio of the molar weight consumption (mmole quantity) of described (R)-1-(1-naphthyl) ethamine, the volume milliliter number of the organic solvent such as used is 2.0,3.0,4.0 or 5.0 with the ratio of the mmole number of (R)-1-(1-naphthyl) ethamine, is more preferably 3.0.
Preferably, the temperature of described reductive coupling reaction is 80 DEG C-150 DEG C, is more preferably 120 DEG C.
Preferably, the time of described reductive coupling reaction is 15h-25h, is more preferably 20h.
In order to illustrate the present invention further, below in conjunction with embodiment, the preferred embodiments of the invention are described.But be to be understood that; these describe just to further illustrate the features and advantages of the present invention; instead of limiting the scope of the invention, those of ordinary skill in the art, not making the every other embodiment obtained under creative work prerequisite, belong to the scope of protection of the invention.The experimental technique of unreceipted actual conditions in the following example, usually according to the normal condition of this area or carry out according to the condition that manufacturer advises.
Unless otherwise defined, all specialties used herein and scientific words and one skilled in the art the same meaning be familiar with.In addition, any method similar or impartial to described content and material all can be applicable in the inventive method.The use that preferred implementation method described herein and material only present a demonstration.
The material used for the synthesis of cinacalcet in the following embodiment of the present invention and reagent are bought in following Reagent Company respectively:
(R)-1-(1-naphthyl) ethamine (C
12h
13n, > 99.0%), 3-(3-trifluoromethyl) propionic acid (C
10h
9f
3o
2, > 98.0%), triethyl-boron (C
6h
15b, 99%), phenylo boric acid (C
6h
7bO
2, 99%), 3,4,5-trifluoro-benzene boron (C
6h
4bF
3o
2, 98%), 2,3,4,5-tetra fluoro benzene boric acid (C
6h
3bF
4o
2, 97%), phenyldimethylsilane (Et
2meSiH, 97%), diethylsilane (Et
2siH
2, 98%), diphenyl silane (Ph
2siH
2, 99%), phenyl silane (PhSiH
3, 98%), diethylene glycol dimethyl ether (C
6h
14o
3, 99.5%) all buy from lark prestige chemical reagents corporation.
Ethyl acetate (99.5%), sodium hydroxide (NaOH, 96.0%), anhydrous sodium sulphate (Na
2sO
4, 99.0%), toluene (C
7h
8, 99.5%) buy from traditional Chinese medicines chemical reagents corporation.
M-xylene (C
8h
10, 99.0%), sym-trimethylbenzene (C
9h
12, 97.0%), three (pentafluorophenyl group) boron (B (C
6f
5)
3, 97%) all buy from TCI company.
4-tert-butyl benzyl amine (C
11h
17n, 98%), 1-naphthoyl chloride (C
11h
7clO, 98.0%), n-butyl ether (C
8h
18o, 99%), poly-(methyl hydrogen siloxane) (CP) all buys from Alfa Aesar company.
1h-NMR,
13c-NMR and
19f-NMR spectrogram all obtains in Bruker Avance 400 nuclear magnetic resonance analyser.
Embodiment
Embodiment 1
In Schlenk reaction tubes (Beijing Xin Weier glassware company limited of 10mL, F891410 reaction tubes, capacity 10mL, ground 14/20) in add 0.005mmol tri-(pentafluorophenyl group) boron, use argon replaces inner air tube, then under argon atmosphere, add 1.5mL n-butyl ether and 2.0mmol phenyl silane and stir (using IKA magnetic stirring apparatus, RCT basic model, stirring velocity 500 revs/min).Then 0.5mmol (R)-1-(1-naphthyl) ethamine and 1.0mmol 3-(3-trifluoromethyl) propionic acid is added.Heat 10h at 120 DEG C after, be cooled to room temperature.With sodium hydroxide solution (3M; 3mL) cancellation, add ethyl acetate (3mL), after stirred at ambient temperature 3h, extraction into ethyl acetate (2mL x 3), organic phase anhydrous sodium sulfate drying, filter, organic phase is by Rotary Evaporators (Bu Qi company limited of Switzerland, BUCHI Rotary Evaporators R-3) concentrated, then through chromatography column (Beijing Xin Weier glassware company limited, C383040C tool sand plate storage ball chromatography column, 35/20, φ 30mm, effectively long: 500ml) chromatographic separation obtains White crystalline product, productive rate 57%.
Products therefrom is carried out proton nmr spectra
1h-NMR (400MHz, CDCl
3), carbon-13 nmr spectra
13c-NMR (101MHz, CDCl
3) and Enantiomeric excess
19f-NMR (376MHz, CDCl
3) analyze, the spectrogram obtained is respectively as Figure 1-3.Confirm that products therefrom is N-((1R)-1-(1-naphthyl) ethyl)-3-(3-(trifluoromethyl) phenyl) the third-1-amine, i.e. cinacalcet thus.
1H NMR(400MHz，CDCl
3)δ8.14(d，J＝8.1Hz，1H)，7.89(d，J＝7.5Hz，1H)，7.77(d，J＝8.2Hz，1H)，7.71(d，J＝7.1Hz，1H)，7.56-7.46(m，3H)，7.44-7.26(m，4H)，4.70(q，J＝6.4Hz，1H)，3.07(br，1H)，2.74-2.57(m，4H)，1.92-1.84(m，2H)，1.55(d，J＝6.6Hz，3H).
13C NMR(101MHz，CDCl
3)δ143.10(s)，140.96(s)，134.09(s)，131.88(q，J＝0.9Hz)，131.37(s)，130.69(q，J＝31.8Hz)，129.14(s)，128.81(s)，127.42(s)，125.82(s)，125.72(s)，125.50(s)，125.15(q，J＝3.8Hz)，124.46(d，J＝303.5Hz)，123.02(s)，122.81(s)，122.75(q，J＝3.9Hz)，53.86(s)，47.34(s)，33.50(s)，31.86(s)，23.62(s).
19F NMR(376MHZ，CDCl
3)δ-62.53.
Embodiment 2
Carry out with the program identical with embodiment 1, after just reaction mixture being heated 18h at 120 DEG C, be cooled to room temperature.Be separated through identical aftertreatment and obtain White crystalline product, productive rate 81%.
Through proton nmr spectra, carbon-13 nmr spectra and Enantiomeric excess analysis, confirmation products therefrom is N-((1R)-1-(1-naphthyl) ethyl)-3-(3-(trifluoromethyl) phenyl) the third-1-amine, i.e. cinacalcet.
Embodiment 3
Carry out with the program identical with embodiment 1, after just reaction mixture being heated 20h at 120 DEG C, be cooled to room temperature.Be separated through identical aftertreatment and obtain White crystalline product, productive rate 88%.
Through proton nmr spectra, carbon-13 nmr spectra and Enantiomeric excess analysis, confirmation products therefrom is N-((1R)-1-(1-naphthyl) ethyl)-3-(3-(trifluoromethyl) phenyl) the third-1-amine, i.e. cinacalcet.
Embodiment 4
Carry out with the program identical with embodiment 1, after just reaction mixture being heated 24h at 120 DEG C, be cooled to room temperature.Be separated through identical aftertreatment and obtain White crystalline product, productive rate 89%.
Through proton nmr spectra, carbon-13 nmr spectra and Enantiomeric excess analysis, confirmation products therefrom is N-((1R)-1-(1-naphthyl) ethyl)-3-(3-(trifluoromethyl) phenyl) the third-1-amine, i.e. cinacalcet.
Embodiment 5
Carry out with the program identical with embodiment 3, just change the 1.5mL n-butyl ether being wherein used as organic solvent into 2.0mL toluene, after reaction mixture is heated 20h at 120 DEG C, be cooled to room temperature.Be separated through identical aftertreatment and obtain White crystalline product, productive rate 71%.
Through proton nmr spectra, carbon-13 nmr spectra and Enantiomeric excess analysis, confirmation products therefrom is N-((1R)-1-(1-naphthyl) ethyl)-3-(3-(trifluoromethyl) phenyl) the third-1-amine, i.e. cinacalcet.
Embodiment 6
Carry out with the program identical with embodiment 3, just change the 1.5mL n-butyl ether being wherein used as organic solvent into 1.0mL m-xylene, after reaction mixture is heated 20h at 120 DEG C, be cooled to room temperature.Be separated through identical aftertreatment and obtain White crystalline product, productive rate 67%.
Through proton nmr spectra, carbon-13 nmr spectra and Enantiomeric excess analysis, confirmation products therefrom is N-((1R)-1-(1-naphthyl) ethyl)-3-(3-(trifluoromethyl) phenyl) the third-1-amine, i.e. cinacalcet.
Embodiment 7
Carry out with the program identical with embodiment 3, just change the 1.5mL n-butyl ether being wherein used as organic solvent into 1.0mL sym-trimethylbenzene, after reaction mixture is heated 20h at 120 DEG C, be cooled to room temperature.Be separated through identical aftertreatment and obtain White crystalline product, productive rate 65%.
Through proton nmr spectra, carbon-13 nmr spectra and Enantiomeric excess analysis, confirmation products therefrom is N-((1R)-1-(1-naphthyl) ethyl)-3-(3-(trifluoromethyl) phenyl) the third-1-amine, i.e. cinacalcet.
Embodiment 8
Carry out with the program identical with embodiment 3, just change the 1.5mL n-butyl ether being wherein used as organic solvent into 3.0mL Isosorbide-5-Nitrae-dioxane, after reaction mixture is heated 20h at 120 DEG C, be cooled to room temperature.Be separated through identical aftertreatment and obtain White crystalline product, productive rate 79%.
Through proton nmr spectra, carbon-13 nmr spectra and Enantiomeric excess analysis, confirmation products therefrom is N-((1R)-1-(1-naphthyl) ethyl)-3-(3-(trifluoromethyl) phenyl) the third-1-amine, i.e. cinacalcet.
Embodiment 9
Carry out with the program identical with embodiment 3, just the 2.0mmol phenyl silane being wherein used as reductive agent is replaced with 2.5mmol diphenyl silane, after reaction mixture is heated 20h at 130 DEG C, be cooled to room temperature.Be separated through identical aftertreatment and obtain White crystalline product, productive rate 64%.
Through proton nmr spectra, carbon-13 nmr spectra and Enantiomeric excess analysis, confirmation products therefrom is N-((1R)-1-(1-naphthyl) ethyl)-3-(3-(trifluoromethyl) phenyl) the third-1-amine, i.e. cinacalcet.
Embodiment 10
Carry out with the program identical with embodiment 3,1.0mmol 3-(3-trifluoromethyl) propionic acid just added changes 0.75mmol 3-(3-trifluoromethyl) propionic acid into, is cooled to room temperature after reaction mixture is heated 24h at 120 DEG C.Be separated through identical aftertreatment and obtain White crystalline product, productive rate 68%.
Through proton nmr spectra, carbon-13 nmr spectra and Enantiomeric excess analysis, confirmation products therefrom is N-((1R)-1-(1-naphthyl) ethyl)-3-(3-(trifluoromethyl) phenyl) the third-1-amine, i.e. cinacalcet.
Embodiment 11
Carry out with the program identical with embodiment 3,1.0mmol 3-(3-trifluoromethyl) propionic acid just added changes 1.25mmol 3-(3-trifluoromethyl) propionic acid into, is cooled to room temperature after reaction mixture is heated 24h at 120 DEG C.Be separated through identical aftertreatment and obtain White crystalline product, productive rate 79%.
Through proton nmr spectra, carbon-13 nmr spectra and Enantiomeric excess analysis, confirmation products therefrom is N-((1R)-1-(1-naphthyl) ethyl)-3-(3-(trifluoromethyl) phenyl) the third-1-amine, i.e. cinacalcet.
Above a kind of method of synthesizing cinacalcet provided by the present invention is described in detail.Apply specific case herein to set forth the principle of invention and embodiment, the explanation of above embodiment just understands method of the present invention and core concept thereof for helping.It should be pointed out that for those skilled in the art, under or else departing from the prerequisite of the principle of the invention, can also carry out some improvement and modification to the present invention, these improve and modify and also fall in the protection domain of the claims in the present invention.
Claims (10)
1. synthesize a method for cinacalcet, described method comprises:
By (R)-1-(1-naphthyl) ethamine of formula (I)
With 3-(3-trifluoromethyl) propionic acid of formula (II)
In organic solvent, take organic silane compound as reductive agent, be that catalyzer issues raw reductive coupling reaction at nonmetal boron compound, and obtain the cinacalcet product of formula (III),
2. the method for synthesis cinacalcet according to claim 1, is characterized in that, the ratio of the molar weight of described 3-(3-trifluoromethyl) propionic acid and described (R)-1-(1-naphthyl) ethamine is 1.0-2.5.
3. the method for synthesis cinacalcet according to claim 1, is characterized in that, described nonmetal boron compound is phenylo boric acid, 3,4,5-trifluoro-benzene boric acid, 2,3, at least one in 4,5-tetra fluoro benzene boric acid, triethyl-boron, three (pentafluorophenyl group) boron.
4. the method for synthesis cinacalcet according to claim 1, it is characterized in that, described organic silane compound is at least one in triethyl silicane, phenyldimethylsilane, diphenyl silane, diethylsilane, poly-(methyl hydrogen siloxane), phenyl silane.
5. the method for synthesis cinacalcet according to claim 1, is characterized in that, described organic solvent is at least one in toluene, m-xylene, sym-trimethylbenzene, diethylene glycol dimethyl ether, Isosorbide-5-Nitrae-dioxane, tetrahydrofuran (THF), n-butyl ether.
6. the method for synthesis cinacalcet according to claim 3, is characterized in that, the ratio of the described nonmetal boron compound of use and the molar weight of described (R)-1-(1-naphthyl) ethamine is 0.005-0.02.
7. the method for synthesis cinacalcet according to claim 4, is characterized in that, the ratio of the molar weight of described organic silane compound and described (R)-1-(1-naphthyl) ethamine is 3.0-5.0.
8. the method for synthesis cinacalcet according to claim 5, is characterized in that, the ratio of the volume ml quantity of described organic solvent and the mmole quantity of described (R)-1-(1-naphthyl) ethamine is 2.0-5.0.
9. the method for synthesis cinacalcet according to any one of claim 1 to 8, is characterized in that, the temperature of described reductive coupling reaction is 80 DEG C-150 DEG C.
10. the method for synthesis cinacalcet according to any one of claim 1 to 8, is characterized in that, the time of described reductive coupling reaction is 15h-25h.
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| CN108409818A (en) * | 2018-05-16 | 2018-08-17 | 新乡拓新药业股份有限公司 | A kind of method of synthesizing cytimidine nucleosides |
| CN109721477A (en) * | 2018-12-25 | 2019-05-07 | 龙岩学院 | Utilize the method for dicarboxylic acids preparation dialdehyde compounds |
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| CN104479724A (en) * | 2014-11-19 | 2015-04-01 | 中国科学技术大学 | Method for preparing hydrocarbon liquid fuel from higher fatty acid and/or ester thereof by virtue of nonmetal catalysis |
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| WO2008035381A2 (en) * | 2006-09-22 | 2008-03-27 | Ind-Swift Laboratories Limited | Process for the preparation of amine derivatives as calcimimetics |
| CN104479724A (en) * | 2014-11-19 | 2015-04-01 | 中国科学技术大学 | Method for preparing hydrocarbon liquid fuel from higher fatty acid and/or ester thereof by virtue of nonmetal catalysis |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108409818A (en) * | 2018-05-16 | 2018-08-17 | 新乡拓新药业股份有限公司 | A kind of method of synthesizing cytimidine nucleosides |
| CN108409818B (en) * | 2018-05-16 | 2020-09-11 | 新乡拓新药业股份有限公司 | Method for synthesizing cytosine nucleoside |
| CN109721477A (en) * | 2018-12-25 | 2019-05-07 | 龙岩学院 | Utilize the method for dicarboxylic acids preparation dialdehyde compounds |
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