- Preparation method of terbinafine hydrochloride
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The invention provides a preparation method of terbinafine hydrochloride, which comprises the steps of: carrying out a substitution reaction on N-methyl-1-naphthylamine (II) and (E)-1, 3-dichloropropene (III) in an acid-binding agent A to obtain an N-(3-chloroallyl-1)-methyl-1-naphthylamine (IV) reaction liquid; carrying out condensation reaction on N-(3-chloroallyl-1)-methyl-1-naphthylamine (IV)and 3, 3-dimethyl-1-butyne (V) in the reaction solution under the action of a composite catalyst and an acid-binding agent B to obtain a reaction solution of (E)-N-(6, 6-dimethyl-2-heptene-4-alkynyl)-N-methyl-1-naphthylamine (VI); complexing and washing the reaction solution with ammonia water to obtain an oily substance; and salifying the oily substance in a hydrochloric acid aqueous solution toobtain crude terbinafine hydrochloride, and recrystallizing the crude terbinafine hydrochloride to obtain terbinafine hydrochloride. The preparation method disclosed by the invention does not use an organic solvent, is environment-friendly, low in cost and simple to operate, and is suitable for industrial production.
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Paragraph 0041; 0044-0048; 0051-0055; 0058-0062; 0065-0068
(2020/09/12)
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- Preparation method for improving purity of terbinafine hydrochloride
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The invention discloses a preparation method for improving the purity of terbinafine hydrochloride, and the method comprises the following steps: 1) adding an acid binding agent into water, stirring and dissolving, adding N-methylnaphthylamine and 1-chlorine-6,6-dimethyl-2-heptene-4-alkyne, and cooling to room temperature; adding ethyl acetate for extraction, filtering, adding a hydrochloric acidaqueous solution, stirring, and filtering to obtain crude terbinafine hydrochloride; and 2) purifying the terbinafine hydrochloride, namely adding the crude terbinafine hydrochloride in the step 1) and purified water into a reaction kettle, heating and refluxing to dissolve, cooling to room temperature, and filtering to obtain a finished product of the terbinafine hydrochloride. According to the preparation method of the terbinafine hydrochloride, only water is used as a crystallization solvent and no toxic solvent is used in the final step reaction of the bulk drug, so that potential harm oftoxic organic solvents to human bodies is avoided; moreover, the solvent amount is extremely small, the cost is low, the generated waste liquid is less, the pollution to the environment is reduced, the product purity and yield are high, the reaction operation is simple, the control is easy, the production period is short, and commercial production is facilitated.
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Paragraph 0023-0037
(2019/11/21)
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- PROCESS FOR PREPARING TERBINAFINE
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A process for preparing terbinafine or a salt thereof having high purity.
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Page/Page column 17; 18
(2010/11/27)
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- Preparations for the care nails that contain Terbinafine hydrochloride
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There are provided topical preparations for the care of fingernails and toenails. The preparation is in the form of a varnish solution that contains Terbinafine Hydrochloride as an active ingredient and a vehicle formulated with all or some of the following components: ethyl alcohol, poly (methyl vinyl ether alt maleic acid monobutyl ester) in 50% ethanol solution, and Butylated Hydroxytoluene (BHT). The topical preparation can be applied in such a way as to be spread freely on the fine tissue of the nail. The preparation is comfortable when applied to the patient, and can be applied infrequently, depending on the degree of severity of the infection, and also shows good tolerability.
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Page/Page column 2
(2008/06/13)
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- A PROCESS FOR THE PURIFICATION OF 1-HALO-6,6-DIMETHYL-HEPT-2-ENE-4-YNE
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The invention relates to a process for purification of 1-halo-6,6-dimethyl-hept-2-ene-4-yne of Formula (I), wherein X represents a halogen atom subjecting crude 1-halo-6,6-dimethyl-hept-2-ene-4-yne to distillation under reduced pressure to obtain pure 1-halo-6,6-dimethyl-hept-2-ene-4-yne. This compound is an important intermediate for the production of the widely used antifungal drug Terbinafine.
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Page/Page column 7
(2008/06/13)
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- IMPROVED PROCESS FOR THE PREPARATION OF TERBINAFINE HYDROCHLORIDE AND NOVEL CRYSTALLINE FORM OF TERBINAFINE
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Improved process for the preparation of Terbinafme Hydrochloride compound of formula (I): substantially free of Genotoxic impurity compound of formula (II) and Novel crystalline form of Terbinafine.
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Page/Page column 21
(2010/11/28)
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- Process for the preparation of naphthylmethylamine derivatives
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Disclosed is a process for the preparation of a naphthylmethylamine derivative or a pharmaceutically acceptable salt thereof of Formula I wherein R1 is a lower straight or branched alkyl group and R2 is a lower straight or branched alkyl group, aryl group or araylalkyl group, the process comprising reacting a N-alkyl-1-naphthylmethylamine HCl compound of Formula II: wherein R1 has the aforestated meaning, with a compound of Formula III wherein X is a halogen and R2 has the aforestated meaning in the presence of at least one base and in at least one solvent.
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Page/Page column 3
(2008/06/13)
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- Process for the preparation of terbinafine and salts thereof
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A process for the preparation of Terbinafine and salts thereof by reacting 1-chloro-6,6-dimethylhept-2-en-4-yne and N-methyl-N-(1-naphthylmethyl)amine in a basic aqueous medium is disclosed. Also disclosed is a process for the preparation of 1-chloro-6,6-dimethylhept-2-en-4-yne.
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Page/Page column 6; 10-11
(2008/06/13)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF TERBINAFINE HYDROCHLORIDE
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The present invention relates to an improved process for preparation of terbinafine hydrochloride ,which is (E) - N- Methyl -N-(1-Naphtylmethyl)-6,6-dimethylhept-2-ene-4-ynyl-1-amine has the formula (I), which comprises reacting t-butylacetylene with ethylmagnesium bromide in THF (ii) adding acrolein at a temperature in the range of 0-10o C to get , 6,6-dimethyl-hept-1-ene-4-yne-3-ol, (iii) reacting it with a mixture of phosphorous oxychloride and hydrochloric acid in methanol (iv) extracting the reaction mass with aliphatic/aromatic solvent and removing the solvent (v) reacting the residue with N-(1-naphtylmethyl)methyl amine in the presence of a base to give Terbinafine (vi) adding hydrochloric acid and extracting the Terbinafine Hcl formed with a chlorinated solvent and (vii) recovering the chlorinated solvent under vacuum and adding ethylacetate to separate Terninafine hydrochloride which is filtered and dried.
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Page/Page column 9-10
(2010/02/14)
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- A PROCESS FOR THE SYNTHESIS OF TERBINAFINE AND DERIVATIVES THEREOF
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The present invention relates to a synthetic method for terbinafine and analogues thereof using metal catalysts, preferably Ni (II) salts and/or complexes.
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Page/Page column 37-38
(2010/02/15)
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- PROCESS FOR PREPARING TERBINAFINE BY USING PLATINUM AS CATALYST
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A process for the preparation of terbinafine, comprising the reaction of a compound of formula (II), or a salt thereof, wherein X is a leaving group, with tert-butylacetylene, in the presence of a platinum catalyst.
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- Process for preparing terbinafine and HCI salt thereof
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Provided are a process for preparing terbinafine or its HCl salt, which comprises: (a) reacting a furan derivative with a base; (b) performing a reductive alkylation of the resulting compound obtained in the step (a) with N-methyl-1-naphthalenemethylamine or its HCl salt; and (c) purifying the resulting compound obtained in the step (b).
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- Process for the preparation of terbinafine
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A process for the preparation of terbinafine which comprises the reaction of tert-butylacetylene with a compound of formula (II) characterized in that the reaction is carried out in the presence of copper (I) salts and of a base, in the absence of palladium.
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- A process for the preparation of terbinafine
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A process for the preparation of terbinafine which comprises the reaction of tert-butylacetylene with a compound of formula (II)???characterized in that the reaction is carried out in the presence of copper (I) salts and of a base, in the absence of palladium.
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- PROCESS FOR PRODUCING ENYNE DERIVATIVES
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A process for producing an enyne derivative, and intermediate, which is useful for preparing compounds showing strong inhibiting activities against squalane.e-poxidase of Eumycetes and strong anti-cholesterol ac-tivities. The process comprises reacting a compound of the formula:
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