- Synthesis method of doxepin hydrochloride
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The invention relates to a synthetic method of doxepin hydrochloride. The method comprises the following steps: (1) phosphites react with 3 - chlorine -1 - (N, N - dimethyl) propylamine to obtain 3 - (N, N - dimethyl) propyl phosphate, or a salt thereof with hydrochloric acid to obtain 3 - (N, N - dimethyl) propyl phosphate hydrochloride. (2) Reaction of 3 - (N, N -dimethyl) propyl phosphate or its hydrochloride with 6, 11 -dihydrodibenzo [b, e] oxepin -11 - ketone under strong base conditions Wittig to obtain doxorubicin. (3) The multi-plug is subjected to salt formation reaction with hydrochloric acid to prepare the doxorubicin hydrochloride. In 1st-step reaction step, the yield of the alkyl phosphate product prepared by adopting the reaction is high, thereby ensuring the yield and purity of the final product hydrochloride. Compared with the prior art, the method has the advantages of simple process, low production cost, less process steps and the like.
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- Improved synthesis method of doxepin hydrochloride
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The invention relates to an improved synthesis method of doxepin hydrochloride. The method comprises the following steps: (1) reacting triphenylphosphine with 3 - chlorine -1 - (N, N - dimethyl) propylamine to prepare (3 - (dimethylamino) propyl) triphenyl phosphine chloride. (2) Reaction of (3 - (dimethylamino) propyl) triphenyl phosphine chloride and 6, 11 -dihydrodibenzo [b, e] oxepin -11 - ketone under a strong base condition to Wittig prepare a doxorubicin. (3) The multi-plug is subjected to salt formation reaction with hydrochloric acid to prepare the doxorubicin hydrochloride. The second Reaction is adopted in Wittig-step reaction, so that the reaction is simpler, the requirements for water and reaction equipment of the solvent and the raw materials are lower, and the repetition rate is higher. Compared with the prior art, the method has the advantages of simple process, low production cost, less process steps and the like.
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Paragraph 0041-0055; 0066-0083; 0090-0095
(2021/11/19)
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- Refining method of doxepin hydrochloride
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The invention belongs to the field of medicine synthesis, and relates to a refining method of doxepin hydrochloride. The refining method of doxepin hydrochloride comprises the following steps: adding a doxepin hydrochloride crude product into water, adjusting the pH value with alkali liquor, extracting with dichloromethane, and spin-drying an organic phase to obtain free doxepin. The method comprises the following steps: dissolving free doxepin in a mixed solvent of diethyl ether and ethanol, adding maleic acid in a controlled temperature range, and stirring to separate out doxepin maleate; adding doxepin maleate into water, adjusting the pH value with alkali liquor, extracting with dichloromethane, and spin-drying an organic phase to obtain free doxepin; dropwise adding isopropyl ether hydrogen chloride into the free doxepin, stirring and crystallizing to obtain doxepin hydrochloride. The Z-configuration doxepin hydrochloride content of the product obtained by the method is 17%-18.5%.
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Paragraph 0025; 0028; 0031; 0034; 0037; 0040
(2021/05/01)
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- Synthetic method of doxepin hydrochloride
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The invention discloses a synthetic method of doxepin hydrochloride. The synthetic method comprises the following steps: using N, N-dimethyl-3-chloropropylamine as an initial raw material, carrying out Grignard reaction, carrying out addition reaction on the reaction product and 6, 11-dihydrodibenzo [b, e] oxepine-11-ketone, and sequentially carrying out elimination reaction and salifying reactionto synthesize the final product. According to the method, high-purity doxepin hydrochloride can be obtained through four-step synthesis, a substitution reaction is not needed, and the yield of the prepared product is high. Compared with the existing synthesis process, the method has the advantages of few synthesis steps, simple process, short production period, low cost and the like.
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Paragraph 0036; 0044-0046; 0049; 0053; 0055; 0059; 0061; 006
(2020/12/30)
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- Iron(II) promoted direct synthesis of dibenzo[b,e]oxepin-11(6H)-one derivatives with biological activity. A short synthesis of doxepin
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A novel and efficient synthesis of dibenzo[b,e]oxepin-11(6H)-ones by direct intramolecular ortho-acylation from readily available 2-(phenoxymethyl)benzoic acids was developed. The method takes advantage of a newly developed cooperative system consisting of sustainable FeCl2 and Cl2CHOCH3 as the key components. This methodology is compatible with a wide variety of functional groups in good to excellent yields and high regioselectivity. The synthetic application of new protocol was extended to the synthesis of known tricyclic drug doxepin as well as a small library of oxepin based derivatives. For the first time, the obtained dibenzo[b,e]oxepinone derivatives were evaluated for their biological activities on the free-living nematode Caenorhabditis elegans as an effective and cost-efficient model system for anthelmintic discovery.
- Scoccia, Jimena,Castro, M. Julia,Faraoni, M. Belén,Bouzat, Cecilia,Martín, Víctor S.,Gerbino, Darío C.
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p. 2913 - 2922
(2017/04/26)
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- A to phthaldialdehyde as the raw material to synthesize method of doxepin hydrochloride (by machine translation)
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This invention discloses in a to phthaldialdehyde as the raw material to synthesize method of doxepin hydrochloride. The method comprises in a wide range of sources phthaldialdehyde as the starting material, reaction by sequentially connie Zha Luo, intramolecular esterification, substituted, cyclized, nucleophilic addition, elimination reactions, nucleophilic substitution, pro-nuclear substituted, and in the reaction, to obtain liu Danhuang pyridine. In section 8 step in the nucleophilic substitution reaction steps, yu Mi using organic lithium compound in the solvent, so that the organic compound forming ammonium lithium salt with dimethylamine , Then this ammonium lithium salt for carrying out the alkylation reaction with halo, improve the yield of the addition, the ultimate so as to guarantee the yield and purity of doxepin hydrochloride. Phthaldialdehyde cheap, so as to reduce the production cost. (by machine translation)
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- Method for preparing doxepin hydrochloride using o-halogen methyl methyl benzoate as raw material
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The present invention discloses a method for preparing doxepin hydrochloride using o-halogen methyl methyl benzoate as a raw material. In the method, o-halogen methyl methyl benzoate which is wide in source is used as a starting raw material, and sulfasalazine is obtained through substitution, hydrolysis, cyclization, nucleophilic addition, elimination reaction, nucleophilic substitution and neutralization reaction. The method comprises: during a nucleophilic substitution reaction obtained in the seventh step, using an organic lithium compound in an ether solution, so that the organic lithium compound and dimethylamine form an ammonium lithium salt (the formula is as shown in the description); then conducting an alkylation reaction on the ammonium lithium salt and a halide to improve the yield of tertiary amine, thereby ensuring the yield and purity of doxepin hydrochloride.
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- A chemoselective deoxygenation of N-oxides by sodium borohydride-Raney nickel in water
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A simple and convenient protocol for deoxygenation of aliphatic and aromatic N-oxides to the corresponding amines in good to excellent yield using sodium borohydride-Raney nickel in water is reported. Other functional moieties such as alkenes, halides, ethers, and amides are unaffected under the present reaction condition.
- Gowda, Narendra B.,Rao, Gopal Krishna,Ramakrishna, Ramesha A.
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experimental part
p. 5690 - 5693
(2010/11/05)
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- ULTRA LOW DOSE DOXEPIN AND METHODS OF USING THE SAME TO TREAT SLEEP DISORDERS
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The invention relates to doxepin, pharmaceutically acceptable salts and prodrugs of doxepin; compositions containing the same, and the use of any of the aforementioned for the treatment of sleep disorders.
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Page/Page column 22
(2008/12/05)
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- METHODS OF USING LOW-DOSE DOXEPIN FOR THE IMPROVEMENT OF SLEEP
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Methods of treating sleep disorders by administration of low doses of doxepin in individuals seeking sustained efficacy or in need of avoiding weight gain, rebound insomnia, or sedative tolerance resulting from doxepin treatment.
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Page/Page column 23; 24
(2008/12/07)
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- Methods of using low-dose doxepin for the improvement of sleep
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Methods of preventing early awakenings, and improving sleep efficiency in hours 7 and 8 of a period of sleep, by administration of low doses of doxepin (e.g., 1-6 mg).
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Page/Page column 11
(2008/06/13)
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- N-DESMETHYL-DOXEPIN AND METHODS OF USING THE SAME TO TREAT SLEEP DISORDERS
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The invention relates to desmethyldoxepin, isomers of desmethyldoxepin, and pharmaceutically acceptable salts and prodrugs of desmethyldoxepin; compositions containing the same, and the use of any of the aforementioned for the treatment of sleep disorders.
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Page/Page column 18-20
(2010/11/29)
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