CN101993379A - Novel preparation method of cinacalcet hydrochloride - Google Patents
Novel preparation method of cinacalcet hydrochloride Download PDFInfo
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- CN101993379A CN101993379A CN2010105310792A CN201010531079A CN101993379A CN 101993379 A CN101993379 A CN 101993379A CN 2010105310792 A CN2010105310792 A CN 2010105310792A CN 201010531079 A CN201010531079 A CN 201010531079A CN 101993379 A CN101993379 A CN 101993379A
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Abstract
The invention discloses a novel preparation method of cinacalcet hydrochloride, belonging to the technical filed of preparation of cinacalcet hydrochloride and comprising the steps of: firstly, with 1-acetonaphthone (II) as a raw material, introducing a chiral reagent, and reducing with sodium borohydride to obtain a compound (III); secondly, dissolving the compound (III) into a proper solvent, and reacting with 3-propiolic halide to obtain a compound (IV); thirdly, adding a proper catalyst into the obtained compound (IV) in a solvent at a certain temperature, and carrying out a coupling reaction with meta-chlorobenzotrifluoride to generate a compound (V); and fourthly, reducing the obtained compound (V) with a proper reducing agent and acidizing with hydrochloric acid to obtain the cinacalcet hydrochloride (I). The cinacalcet hydrochloride is synthesized chirally, and has the advantages of special reaction course, good selectivity, high yield, less reaction steps, safe and simple operation and little environment pollution. The raw material used in the reaction course is easy to obtain, has lower production cost and high optical purity, and is suitable for industrialized production.
Description
Technical field:
The present invention relates to a kind of new preparation method of cinacalcet hydrochloride who is used for the treatment of the hyperparathyroidism medicine.The preparing technical field that belongs to cinacalcet hydrochloride.
Background technology:
2004, FDA Food and Drug Administration ratified the secondary hyperparathyroidism that can treat the chronic nephropathy dialysis patient by Amgen production, can treat the too much new drug cinacalcet of Parathyroid carninomatosis people blood calcium again.Cinacalcet hydrochloride is N-[1-(R)-(-)-naphthyl] ethyl]-3-[3-(trifluoromethyl) phenyl]-the international name of 1-propylamin hydrochloride, CAS number is 364782-34-3, chemical formula is C
22H
22F
3NHCl, its structural formula is as follows:
Cinacalcet hydrochloride is the agent of a kind of oral plan calcium, is first kind of this type of medicine of being ratified by FDA.In the U.S., it is with title
Sell; In Europe, it is with name
With
Disappear and sell.It has been granted to be used for the treatment of chronic's the Secondary cases hyperthyroidism of dialysis and the hypercalcinemia that treatment suffers from the thyroid carcinoma patient.
United States Patent (USP) the 6th, 211 has been described cinacalcet and pharmaceutical acceptable acid muriate additive salt thereof, but the embodiment of any preparation cinacalcet or cinacalcet hydrochloride is not provided for No. 244.
Drugs 2002,27 (9), and 831-836 discloses according to United States Patent (USP) the 6th, 211, the general method of describing in No. 244 prepares the synthetic schemes of cinacalcet hydrochloride, and promptly naphthalene ethylamine and 3-(3-trifluoromethyl) propionic acid is through the catalysis of isopropyl titanate, and synthetic route is as follows:
The shortcoming of this technology is: 1. side reaction is serious, and productive rate is low; 2. use the sodium cyanoborohydride that costs an arm and a leg and severe toxicity is arranged as reductive agent, be unfavorable for suitability for industrialized production.In addition, this patent does not illustrate the synthesis technique of important intermediate R-1-naphthalene ethylamine and 3-(3-trifluoromethyl) propionic acid, causes performance difficulty.
International patent is: WO 2008/058235 A2 discloses the technology of other three kinds of synthetic cinacalcets, and synthetic route is as follows respectively:
These three kinds of methods are similar, with Drugs 2002,27 (9), the disclosed route of 831-836 is also roughly the same, but in the embodiment 3 and 4 of WO2008/058235 A2 patent, provided the method with the synthetic R-1-naphthalene ethylamine of 1-acetonaphthone, i.e. 1-acetonaphthone and ammonium formiate reaction obtains the 1-naphthalene ethylamine of racemization, use D (+) Naproxen Base to split again, promptly get (R)-1-naphthalene ethylamine.Synthetic route is as follows:
Though the synthesis step that WO2008/058235 A2 patent provides is more comprehensive, also has many shortcomings: it is serious 1. to generate by product, and obtains the naphthalene ethylamine process and need split, productive rate is lower; 2. used harmful and deleterious reagent in the reaction process to environment, as HOBt (azimidobenzene), DCC (dicyclohexylcarbodiimide) etc.; 3. product will be purified through separating for several times, and step is various, is unfavorable for suitability for industrialized production.
Though the report about the cinacalcet synthetic method is a lot, its limitation is all arranged, low as productive rate, step is various, the poisonous or harm environment etc. of the reagent of use.
Summary of the invention:
The objective of the invention is to, a kind of yield height that has is provided, operational safety is simple, and production cost is low, and environmental pollution is little, is applicable to the new preparation method of cinacalcet hydrochloride of suitability for industrialized production.
The present invention realizes above-mentioned purpose by following technical solution:
The preparation method that a kind of cinacalcet hydrochloride is new, described cinacalcet hydrochloride is the Chiral Amine compounds, it is characterized in that: it may further comprise the steps:
The first step: with the 1-acetonaphthone
Be starting raw material, with suitable dissolution with solvents (quantity of solvent is 8～12mL/g 1-acetonaphthone), under 20～200 ℃ of temperature condition, introduce chiral reagent and isopropyl titanate (mol ratio of chiral reagent and 1-acetonaphthone is 1: 1～2: 1), (mol ratio of isopropyl titanate and 1-acetonaphthone is 0.5: 1～2: 1), use sodium borohydride reduction (mol ratio of sodium borohydride and 1-acetonaphthone is 1: 1～2: 1) then, promptly obtain compound (III)
The preferred temperature of described temperature of reaction is 50～120 ℃, and optimum temps is 60～80 ℃;
Described suitable solvent includes but are not limited to a kind of in the following material: methyl alcohol, ethanol, Virahol, tetrahydrofuran (THF), normal heptane, toluene, methyl tertiary butyl ether;
Described chiral reagent includes but are not limited to a kind of in the following material: the amine of chirality, the acid amides of chirality, the amino acid of chirality; Be optimal selection wherein with chirality tertiary butyl sulfinyl amine;
Second step: the compound (III) that obtains in the first step is dissolved in (quantity of solvent is 8～12mL/g compound III) in the suitable solvent, under 0～100 ℃ of temperature condition, alkalization (alkali of adding is 1.0～2.0 equivalents), add 3-propiolic halide (mol ratio of 3-propiolic halide and compound III is 1: 1～2: 1) again, reaction obtains compound (IV)
Described suitable reagent includes but are not limited to a kind of in the following material: methyl alcohol, ethanol, Virahol, methyl tertiary butyl ether, ether, ethyl acetate, tetrahydrofuran (THF);
The preferred temperature of described temperature of reaction is 20～80 ℃, and optimum temps is 40～60 ℃;
The compound that is used for alkalizing includes but are not limited to a kind of in the following material: sodium hydride, sodium methylate, sodium ethylate, n-propyl alcohol, sodium isopropylate, propyl carbinol sodium, sodium tert-butoxide, sodium hydroxide, potassium hydroxide, yellow soda ash, sodium bicarbonate; Sodium hydride wherein, sodium tert-butoxide, potassium tert.-butoxide are optimal selection;
Described 3-propiolic halide is 3-chloroallylene or 3-propargyl bromide;
The 3rd step: with the compound (IV) that obtains in second step, under 20～180 ℃ of temperature, be dissolved in (quantity of solvent is 8～12mL/g compound IV) in the suitable solvent, halogen phenylfluoroform (mol ratio of a halogen phenylfluoroform and compound IV is 0.8: 1～2: 1) between adding again, add diethylamine and appropriate catalyst (mol ratio of diethylamine and compound IV is 0.8: 1～2: 1), (the catalyzer add-on is 0.5～2 mole of catalysis equivalent) again, promptly obtain compound (V)
The preferred temperature of described temperature of reaction is 50～160 ℃, and optimum temps is 50～80 ℃;
Described suitable reagent includes but are not limited to a kind of in the following material: methyl alcohol, ethanol, Virahol, methyl tertiary butyl ether, glycol dimethyl ether, ethyl acetate, tetrahydrofuran (THF);
Described appropriate catalyst includes but are not limited to a kind of in the following material: palladium, Palladous chloride, palladium iodide, cuprous iodide;
Described halogen phenylfluoroform is: a fluoride trifluoro toluene, meta-chlorobenzotrifluoride, iodine phenylfluoroform between a 5 bromine benzotrifluoride reaches;
The 4th step: with the suitable solvent (quantity of solvent is 8～12mL/g compound V) of the middle adding of compound (V) that the 3rd step obtained, (pressure is 5Kg/cm to feed hydrogen under-20～200 ℃ temperature
2) and add catalyzer (catalyzer and compound V weight ratio are 1: 4.5～1: 5.5), in the reduzate that obtains, add hydrochloric acid (mol ratio of hydrochloric acid and compound V is 1: 1～2: 1) then, promptly obtain target product cinacalcet hydrochloride (I)
Described suitable solvent includes but are not limited to a kind of in the following material: methyl alcohol, ethanol, Virahol, acetone, ethyl acetate, ether, methyl tertiary butyl ether, normal heptane, toluene, tetrahydrofuran (THF);
The preferred temperature of described temperature of reaction is 0～100 ℃, and optimum temps is 50～70 ℃;
Described suitable reducing catalyst includes but are not limited to a kind of in the following material: palladium carbon, metal platinum, metallic nickel, metal Ru, metal rhodium.
The synthesis route that cinacalcet hydrochloride of the present invention (I) is described with chemical structural formula is as follows:
The present invention's beneficial effect compared with prior art is:
1, the present invention is synthetic for chirality, reaction circuit uniqueness, and selectivity is good, the yield height, reactions steps is few, and process choice is reasonable, and is simple to operate.
2, raw material sources of the present invention are convenient, and cost is low; Environmental pollution is little, and operational safety is applicable to suitability for industrialized production.
Embodiment:
Below in conjunction with a specific embodiment the present invention is further described, but the present invention not only is confined to following embodiment.
The first step: preparation compound (III)
In the round-bottomed flask of 100mL, add 1-acetonaphthone (1.7g),, add (R)-tertiary butyl sulfinyl amine (2.2g) again with tetrahydrofuran (THF) (20mL) dissolving, reaction mixture is heated to 70 ℃, in flask, add the 2.8g isopropyl titanate then, after about 10min adds, insulation reaction 22h.Finish with the TLC monitoring reaction, be cooled to about 0 ℃ again.Sodium borohydride (0.5g) is dissolved in tetrahydrofuran (THF) (3mL), is cooled to 0 ℃, slowly be added in the above-mentioned reaction mixture, about 10min after adding, is heated to normal temperature and insulated and stirred 5h.After the TLC monitoring reaction finishes, be cooled to 0 ℃.Restir 5min, the suspension liquid that obtains is filtered, and filter cake washs with ethyl acetate (10mL), and washings adds saturated NaCl (10mL), water is used ethyl acetate extraction three times again, the used ethyl acetate amount of each extraction is 10mL, merges organic phase and uses dried over sodium sulfate, filters, filtrate normal temperature concentrating under reduced pressure, and dry, promptly get compound (III) 2.15g, yield is 78%.
Second step: preparation compound (IV)
Other gets the round-bottomed flask of a 50mL, and the compound (III) that the first step is obtained adds, and with the dissolving of 25mL methyl tertiary butyl ether, is heated to the sodium tert-butoxide that adds 0.8g after 50 ℃, adds 3-chloroallylene 0.9g then, insulated and stirred 3h.The TLC monitoring reaction finishes, and adds water 25mL collection and goes out, and tells organic layer, be cooled to 5 ℃, promptly there is crystal to separate out, keeps this temperature to continue to stir, to be crystallized complete, filter, filter cake is used methyl alcohol 10mL successively, water 10mL washing, decompression (200mmHg) drying, promptly get compound (IV) 2.12g, yield is 68%.
The 3rd step: preparation compound (V)
Get the flask of a clean 50mL, add iodine phenylfluoroform between 3g, use the 10mL dissolve with ethanol, obtain an iodine phenylfluoroform ethanol liquid.The compound (IV) that the last step obtains is used the 25ml dissolve with ethanol, be heated to 80 ℃, to wherein slowly drip got ready between iodine phenylfluoroform ethanol liquid, about 5min of dropping time, add 2 moles of catalysis equivalent palladium and 0.8g diethylamine again, stir about 6h under this temperature.The TLC monitoring reaction finishes, and filters, and filtrate is cooled to 20 ℃, promptly has crystal to separate out, continue to stir 30min, to be crystallized complete, filter, filter cake is used toluene 10mL successively, water 10mL washing, the 200mmHg drying that reduces pressure promptly gets compound (V) 3.01g, and yield is 66%.
The 4th step: preparation compound (I)
The compound (V) that obtains is dissolved in MTBE (30mL), adds the 5%Pd/C of 0.6g, be heated to 60 ℃, stir, then with 5Kg/cm
2Pressure feed hydrogen 4h.After the TLC monitoring reaction finished, with reacting liquid filtering, the filtrate decompression distillation removed and desolvates, again residue is dissolved in tetrahydrofuran (THF) (20mL), stirs, with the aqueous sodium carbonate washing of 30mL10%, layering, tell organic layer, water layer adds methylene dichloride 30mL again, tells organic layer after the layering.Merge organic phase, underpressure distillation adds the acetic acid ethyl dissolution of 5mL in the debris that obtains, add the diethyl ether liquid (20mL) of hydrochloric acid again, stirs 30min, and underpressure distillation obtains crude salt.Add the 3mL ethyl acetate, filter, with cold ethyl acetate washing, 40 ℃ of following vacuum (200mmHg) drying obtains 2.56g cinacalcet hydrochloride white crystalline powder to the white crystal that obtains again, and yield is 65%.
Fusing point: 180～184 ℃.
1H?NMR(CDCl
3-DMSO-d
6)(δppm)：10.62(1H，bs)，10.07(1H，bs)，7.16-8.5(1H，m)，5.19(1H，q)，2.75(2H，t)，2.52(2H，m)，2.28(2H，m)，1.98(3H，d)。
MS(m/z)：358[M+1]。
The present invention adopts chirality synthetic, the synthetic route uniqueness, and selectivity is good, the yield height; Simple to operate, cost is low, pollutes for a short time, is fit to suitability for industrialized production.
Claims (5)
1. preparation method that cinacalcet hydrochloride is new, described cinacalcet hydrochloride is the Chiral Amine compounds, it is characterized in that: it may further comprise the steps:
The first step: with the 1-acetonaphthone is starting raw material, with quantity of solvent is the suitable dissolution with solvents of 8～12mL/g 1-acetonaphthone, under 20～200 ℃ of temperature condition, introduce chiral reagent and isopropyl titanate, the mol ratio of chiral reagent and 1-acetonaphthone is 1: 1～2: 1, and the mol ratio of isopropyl titanate and 1-acetonaphthone is 0.5: 1～2: 1, uses sodium borohydride reduction then, the mol ratio of sodium borohydride and 1-acetonaphthone is 1: 1～2: 1, promptly obtains compound (III)
Second step: the compound (III) that obtains in the first step is dissolved in the suitable solvent that quantity of solvent is 8～12mL/g compound III, under 0～100 ℃ of temperature condition, alkalization, the alkali that adds is 1.0～2.0 equivalents, add 3-propiolic halide (mol ratio of 3-propiolic halide and compound III is 1: 1～2: 1) again, reaction obtains compound (IV)
The 3rd step: with the compound (IV) that obtains in second step, being dissolved in quantity of solvent under 20～180 ℃ of temperature is in the suitable solvent of 8～12mL/g compound IV, halogen phenylfluoroform between adding again, between the mol ratio of halogen phenylfluoroform and compound IV be 0.8: 1～2: 1, add diethylamine and appropriate catalyst again, the mol ratio of diethylamine and compound IV is 0.8: 1～2: 1, and the catalyzer add-on is 0.5～2 mole of catalysis equivalent, promptly obtains compound (V)
The 4th step: with adding quantity of solvent in the compound (V) that obtains in the 3rd step is the suitable solvent of 8～12mL/g compound V, and feeding pressure under-20～200 ℃ temperature is 5Kg/cm
2Hydrogen and add catalyzer, catalyzer and compound V weight ratio are 1: 4.5～1: 5.5, add hydrochloric acid then in the reduzate that obtains, the mol ratio of hydrochloric acid and compound V is 1: 1～2: 1, promptly obtains target product cinacalcet hydrochloride (I)
The synthesis route that cinacalcet hydrochloride of the present invention (I) is described with chemical structural formula is as follows:
2. the new preparation method of a kind of cinacalcet hydrochloride according to claim 1 is characterized in that, in the first step:
The preferred temperature of described temperature of reaction is 50～120 ℃, and optimum temps is 60～80 ℃;
Described suitable solvent comprises a kind of in the following material: methyl alcohol, ethanol, Virahol, tetrahydrofuran (THF), normal heptane, toluene, methyl tertiary butyl ether;
Described chiral reagent comprises a kind of in the following material: the amine of chirality, the acid amides of chirality, the amino acid of chirality; Be the best wherein with chirality tertiary butyl sulfinyl amine.
3. the new preparation method of a kind of cinacalcet hydrochloride according to claim 1 is characterized in that, in second step:
Described suitable reagent comprises a kind of in the following material: methyl alcohol, ethanol, Virahol, methyl tertiary butyl ether, ether, ethyl acetate, tetrahydrofuran (THF);
The preferred temperature of described temperature of reaction is 20～80 ℃, and optimum temps is 40～60 ℃;
The described compound that is used for alkalizing comprises a kind of in the following material: sodium hydride, sodium methylate, sodium ethylate, n-propyl alcohol, sodium isopropylate, propyl carbinol sodium, sodium tert-butoxide, sodium hydroxide, potassium hydroxide, yellow soda ash, sodium bicarbonate, sodium hydride wherein, sodium tert-butoxide, potassium tert.-butoxide are optimal selection;
Described 3-propiolic halide is 3-chloroallylene or 3-propargyl bromide.
4. the new preparation method of a kind of cinacalcet hydrochloride according to claim 1 is characterized in that, in the 3rd step:
The preferred temperature of described temperature of reaction is 50～160 ℃, and optimum temps is 50～80 ℃;
Described suitable reagent comprises a kind of in the following material: methyl alcohol, ethanol, Virahol, methyl tertiary butyl ether, glycol dimethyl ether, ethyl acetate, tetrahydrofuran (THF);
Described appropriate catalyst comprises a kind of in the following material: palladium, Palladous chloride, palladium iodide, cuprous iodide;
Described halogen phenylfluoroform is: a fluoride trifluoro toluene, meta-chlorobenzotrifluoride, iodine phenylfluoroform between a 5 bromine benzotrifluoride reaches.
5. the new preparation method of a kind of cinacalcet hydrochloride according to claim 1 is characterized in that, in the 4th step:
Described suitable solvent comprises a kind of in the following material: methyl alcohol, ethanol, Virahol, acetone, ethyl acetate, ether, methyl tertiary butyl ether, normal heptane, toluene, tetrahydrofuran (THF);
The preferred temperature of described temperature of reaction is 0～100 ℃, and optimum temps is 50～70 ℃;
Described suitable reducing catalyst comprises a kind of in the following material: palladium carbon, metal platinum, metallic nickel, metal Ru, metal rhodium.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102320981A (en) * | 2011-07-19 | 2012-01-18 | 上海泰坦化学有限公司 | Chiral intermediate (S)-1-cyclobutyl ethylamine hydrochloride as well as preparation method and application thereof |
| CN102976953A (en) * | 2011-09-05 | 2013-03-20 | 上海药明康德新药开发有限公司 | Preparation method of chiral alpha-difluoromethyl phenyl ethylamine |
| CN103664577A (en) * | 2012-09-06 | 2014-03-26 | 北京万生药业有限责任公司 | Preparation method of cinacalcet intermediate |
| CN106831441A (en) * | 2017-01-23 | 2017-06-13 | 江苏康思尔医药科技有限公司 | A kind of preparation method of cinacalcet hydrochloride |
| CN109535006A (en) * | 2018-11-30 | 2019-03-29 | 廖艺 | It is a kind of to prepare cinacalcet hydrochloride intermediate and method |
| CN111196759A (en) * | 2018-11-16 | 2020-05-26 | 上海博志研新药物技术有限公司 | Preparation method of cinacalcet hydrochloride and intermediate thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6211244B1 (en) * | 1994-10-21 | 2001-04-03 | Nps Pharmaceuticals, Inc. | Calcium receptor-active compounds |
| WO2008058235A2 (en) * | 2006-11-08 | 2008-05-15 | Dr. Reddy's Laboratories, Ltd. | Processes for the preparation of cinacalcet |
-
2010
- 2010-10-22 CN CN 201010531079 patent/CN101993379B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6211244B1 (en) * | 1994-10-21 | 2001-04-03 | Nps Pharmaceuticals, Inc. | Calcium receptor-active compounds |
| WO2008058235A2 (en) * | 2006-11-08 | 2008-05-15 | Dr. Reddy's Laboratories, Ltd. | Processes for the preparation of cinacalcet |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102320981A (en) * | 2011-07-19 | 2012-01-18 | 上海泰坦化学有限公司 | Chiral intermediate (S)-1-cyclobutyl ethylamine hydrochloride as well as preparation method and application thereof |
| CN102320981B (en) * | 2011-07-19 | 2014-12-31 | 上海泰坦化学有限公司 | Chiral intermediate (S)-1-cyclobutyl ethylamine hydrochloride as well as preparation method and application thereof |
| CN102976953A (en) * | 2011-09-05 | 2013-03-20 | 上海药明康德新药开发有限公司 | Preparation method of chiral alpha-difluoromethyl phenyl ethylamine |
| CN103664577A (en) * | 2012-09-06 | 2014-03-26 | 北京万生药业有限责任公司 | Preparation method of cinacalcet intermediate |
| CN103664577B (en) * | 2012-09-06 | 2015-04-08 | 北京万生药业有限责任公司 | Preparation method of cinacalcet intermediate |
| CN106831441A (en) * | 2017-01-23 | 2017-06-13 | 江苏康思尔医药科技有限公司 | A kind of preparation method of cinacalcet hydrochloride |
| CN111196759A (en) * | 2018-11-16 | 2020-05-26 | 上海博志研新药物技术有限公司 | Preparation method of cinacalcet hydrochloride and intermediate thereof |
| CN111196759B (en) * | 2018-11-16 | 2023-03-24 | 上海博志研新药物技术有限公司 | Preparation method of cinacalcet hydrochloride and intermediate thereof |
| CN109535006A (en) * | 2018-11-30 | 2019-03-29 | 廖艺 | It is a kind of to prepare cinacalcet hydrochloride intermediate and method |
| CN109535006B (en) * | 2018-11-30 | 2022-02-01 | 廖艺 | Intermediate and method for preparing cinacalcet hydrochloride |
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