183319-69-9Relevant articles and documents
Convergent approach for commercial synthesis of gefitinib and erlotinib
Chandregowda, Venkateshappa,Rao, Gudapati Venkateswara,Reddy, Goukanapalli Chandrasekara
, p. 813 - 816 (2007)
An efficient, economical and large-scale convergent synthesis of epidermal growth factor receptor- tyrosine kinase inhibitors gefitinib (1, Iressa) and erlotinib (2, Tarceva) approved by U.S. FDA for the treatment of non-small-cell lung cancer is described. The formation of 4-anilinoquinazolines are achieved in a simple one-pot reaction of suitable forniamidine intermediates and substituted anilines involving Dimroth rearrangement, thereby avoiding the need to make quinazolin-4(3H)-one intermediates, which require a large experimental inputs. Using this process, we have produced drug candidates 1 with overall yield of 66% from 4-methoxy-5-[3-(4-morpholinyl) propoxy]-2-nitrobenzonitrile (3) and 2 with 63% from 4-bis(2-methoxyethoxy)-2-nitrobenzonitrile (6) on a multigram scale.
Improved synthesis of gefitinib and erlotinib hydrochloride- anticancer agents
Chandregowda, Venkateshappa,Rao, Gudapati Venkateswara,Reddy, Goukanapalli Chandrasekara
, p. 3409 - 3415 (2007)
A highly efficient and commercially viable process for the synthesis of 6,7-dihydroxy-4-anilinoquinazoline derivatives gefitinib (1) and erlotinib hydrochloride (2), used for the treatment of non-small cell lung cancer (NSCLC) and pancreatic cancer, is reported. This new process has improved yields and avoids the unstable 4-chloroquinazoline intermediate. The intermediates and final products were characterized by 1H and 13C nuclear magnetic resonance (NMR), mass spectra (MS), and elemental analysis, and purities of final products were determined by high performance liquid chromatogram (HPLC) and potentiometric titration methods. Copyright Taylor & Francis Group, LLC.
Solubility of two polymorphs of erlotinib hydrochloride in isopropanol and acetone from (273.15 to 303.15) K
Lu, Jie,Zhan, Xiaolan,Chen, Lianwei,Zhang, Lijuan,Mao, Shimin
, p. 2665 - 2669 (2014)
In this work the solubility of two polymorphic forms A and B of erlotinib hydrochloride in isopropanol (IPA) and acetone were determined by means of high-performance liquid chromatography (HPLC) in the temperature range from (273.15 to 303.15) K. The experimental data were correlated with the modified Apelblat equation. In particular, the effect of the surfactant Tween 80 on the solubility of both polymorphs was studied as well. The results show that the solubility of both polymorphs generally increases with the temperature, and polymorph A has a higher solubility than polymorph B which indicates that polymorph A is the metastable form. The modified Apelblat equation shows a good agreement with the experimental data with a percent error less than 3 %. Furthermore, the solubility of both polymorphs increases in a linear fashion with increasing the content of Tween 80 in organic solvents, wherein Tween 80 presents a same solubilization capacity to both polymorphs and a higher solubilization capacity in acetone than in IPA.
Preparation method of erbtinib
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Paragraph 0009; 0048-0053, (2020/06/16)
The invention discloses a preparation method of erbtinib. The method comprises the following steps: carrying out a cyclization reaction on a compound represented by formula 1 to obtain a compound represented by formula 2, carrying out a chlorination reaction on the compound of the formula 2 to obtain a compound represented by formula 3, and carrying out a substitution salification reaction on thecompound of the formula 3 to obtain the compound erbtinib represented by formula 4. The preparation method of erbtinib can greatly shorten the production cycle when used for preparing erbtinib hydrochloride, can effectively avoid the defects of long production cycle, serious environmental pollution, unstable intermediate, difficult product purification, complex operation and the like, and has theadvantages of short reaction steps, simple operation, easy reaction, high product purity, high yield and low cost. The addition amount of reactants is properly controlled, the environmental requirements are clear, and a clear and new production direction is provided for process production.
Preparation method of erlotinib hydrochloride
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, (2020/04/01)
The invention relates to a preparation method for erlotinib hydrochloride. The preparation method comprises the following steps: reacting 2-amino-4,5-dimethoxybenzoic acid with formamide to generate acompound 5, carrying out a bromination reaction on the compound 5, and subjecting a bromination product and 3-acetenyl aniline to a reaction and amination to generate a compound 3; and reacting the compound 3 with 48% hydrobromic acid under the action of a catalyst to obtain a compound 2, and reacting the compound 2 with iodoethylmethyl ether under the action of an alkali and the catalyst to generate erlotinib hydrochloride. The method has the advantages of mild conditions, low impurity content, safety, no pollution and environmental protection, and is suitable for industrial production.
The preparation method of the [...] hydrochloride
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Paragraph 0023-0036, (2019/06/11)
The invention provides a preparation method for an erlotinib hydrochloride crystal form. The preparation method is as follows: mixing erlotinib free alkaline with an organic solvent, and dropwise adding concentrated hydrochloric acid under a low-temperature condition to obtain high-purity erlotinib hydrochloride crystal form. The preparation method disclosed by the invention has characteristics of being easy in obtaining of materials, controllable in quality (concentrated hydrochloric acid), good in repeatability, simple to operate, high in yield, low in cost, and high in obtained sample purity, is more suitable for industrial production, and has very high economic benefits.
Preparation method for high-purity erlotinib hydrochloride
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Paragraph 0040-0049, (2019/05/16)
The invention belongs to the field of pharmaceutical synthesis, and provides a method for preparing high-purity erlotinib hydrochloride. The method comprises the following steps: 6,7-di(2-methoxyethoxy)quinazoline-4-one is used as a raw material, chlorination is performed to obtain 4-chloro-6,7-di(2-methoxyethoxy)quinazoline (compound I), refining is performed on the compound I, the refined compound I is reacted with 3-aminophenylacetylene, and therefore the high-purity erlotinib hydrochloride is obtained, wherein the purity obtained by HPLC is 99.85% or more, and the content of an impurity 1and an impurity 2 is less than 0.06%. The method provided by the invention is suitable for industrial large-scale production.
A method for preparing environmental protection of erlotinib hydrochloride
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Paragraph 0086; 0087, (2017/09/26)
The invention discloses an environment-friendly method for preparing high-yield erlotinib hydrochloride. The method comprises the following steps: directly performing cyclic condensation by taking 2-amino-4,5-di(2-methoxy ethyoxyl) ethyl benzoate hydrochloride as a key intermediate, reacting with aminophenylacetylene to generate erlotinib hydrochloride after performing chlorination, and refining to obtain the high-purity erlotinib hydrochloride. The process route provided by the invention is mild in reaction condition and high in yield; the first-class reagent and other reagents harmful to the environment and the operators are not used, the byproduct is few, the aftertreatment is simple and the commercial process can be easily processed.
Synthesis method of erlotinib hydrochloride
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Paragraph 0059-0062, (2017/08/31)
The invention discloses a synthesis method of erlotinib hydrochloride. The synthesis method comprises the following steps: (1) at a first working section: preparing 3-methoxyl-4-hydroxybenzonitrile from vanillin and hydroxylammonium chloride; (2) at a second working section: synthesizing 3,4-dihydroxybenzonitrile; (3) at a third working section: synthesizing 3,4-di(2-methoxyethoxy)phenylacetonitrile; (4) at a fourth section: synthesizing 4,5-di(2-methoxyethoxy)-2-nitrophenylacetonitrile; (5) at a fifth working section: synthesizing 4,5-di(2-methoxyethoxy)-2-aminophenylacetonitrile hydrochloride; and (6) at a sixth working section: synthesizing the erlotinib hydrochloride. The synthesis method of the erlotinib hydrochloride, disclosed by the invention, has the advantages of reasonable design, easiness of obtaining raw materials, relatively low production cost, simplicity and easiness of operation and is suitable for industrial production.
A synthesis method of erlotinib hydrochloride (by machine translation)
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Paragraph 0052; 0053; 0054; 0055, (2017/06/30)
The invention relates to a technical field of drug synthesis, relates to a new synthetic method of erlotinib hydrochloride. The steps are as follows: 1) to acetophenone as a starting material, in the nitration reaction takes place in the mixed between nitro acetophenone; 2) between nitro acetophenone with chlorinated reagent in the organic solvent in the reaction of chloride 1 - chloro - 1 - (3 - nitrophenyl) ethylene; 3) 1 - chloro - 1 - (3 - nitrophenyl) ethylene in the presence of an organic solvent and alkali to obtain between the dehydrochlorination nitrobenzene acetylene; 4) m acetylene through the nitro-selective reduction to obtain between amino acetylene; reduction method as a reducing agent or catalytic hydrogenation reduction; 5) between amino acetylene and 4 - chloro - 6, 7 - b - (2 - methoxyethoxy) quinazoline in reaction of organic solvent to obtain the erlotinib hydrochloride; raw materials of the invention is cheap, low production cost, simple operation, mild reaction conditions and the like, and is suitable for industrial production. (by machine translation)