1269662-73-8

Basic information

• Product Name: (E)-N-[4-[[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolinyl]-3-[(2R)-1-methylpyrrolidin-2-yl]propan-2-enoylamine
• Synonyms: (E)-N-[4-[[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolinyl]-3-[(2R)-1-methylpyrrolidin-2-yl]propan-2-enoylamine
• CAS NO: 1269662-73-8
• Molecular Weight: 583.09
• Mol File: 1269662-73-8.mol

Chemical Properties

• CAS DataBase Reference: (E)-N-[4-[[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolinyl]-3-[(2R)-1-methylpyrrolidin-2-yl]propan-2-enoylamine(CAS DataBase Reference)
• NIST Chemistry Reference: (E)-N-[4-[[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolinyl]-3-[(2R)-1-methylpyrrolidin-2-yl]propan-2-enoylamine(1269662-73-8)
• EPA Substance Registry System: (E)-N-[4-[[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolinyl]-3-[(2R)-1-methylpyrrolidin-2-yl]propan-2-enoylamine(1269662-73-8)

Safety Data

• Hazardous Substances Data: 1269662-73-8(Hazardous Substances Data)

Usage

Uses

Pyrotinib, is a potent and selective EGFR/HER2 dual inhibitor.

Upstream product

• 848139-78-6 6-amino-4-[[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino]-7-ethoxyquinoline-3-carbonitrile 
• 1269662-79-4 diethyl ({[4-({3-chloro-4-[(pyridin-2-yl)methoxy]phenyl}amino)-3-cyano-7-ethoxyquinolin-6-yl]carbamoyl}methyl)phosphonate 
• 852324-28-8 (2R)-1-methylpyrrolidine-2-formaldehyde 
• 69610-40-8 N-(tert-butoxycarbonyl)-L-prolinol 
• 23356-96-9 (S)-1-Pyrrolidin-2-yl-methanol 
• 3554-65-2 (R)-N-methylpyrrolidine-2-methanol 
• 121-88-0 5-Nitro-2-aminophenol 
• 59378-81-3 1-(tert-butoxycarbonyl)prolin-2R-ol 

Downstream Products

• 1397922-62-1 (E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-3-[(2R)-1-methylpyrrolidin-2-yl]prop-2-enamide L-malate 
• 1397922-61-0 (E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-3-[(2R)-1-methylpyrrolidin-2-yl]prop-2-enamide maleate 
• 1397922-61-0 (R,E)-N-(4-(3-chloro-4-(pyridine-2-ylmethoxy)phenylamino)-3-cyano-7-ethoxyquinoline-6-yl)-3-(1-methylpyrrolidinyl-2-yl)acrylamide dimaleate salt 

Relevant articles and documents

Preparation method of pyrrotinib

The invention discloses a preparation method of pyrrotinib, and belongs to the technical field of chemical synthesis of medicines. The preparation method comprises the following steps: 1, preparing R,E-N-(-2-hydroxy- 4-nitrophenyl)-3- (-1-methyl pyrrolidine -2-yl)acrylamide; 2, preparing (R, E)-N -(2-ethoxy -4-nitrophenyl)-3- (1-methyl pyrrolidine -2-yl)acrylamide; 3, preparing (R,E)-N-(4-amino-2-ethoxyphenyl)-3-(1-methylpyrrolidine-2-yl)acrylamide; 4, preparing (2E)-N -(4-amino- 3-cyano- 7-ethoxy quinoline -6-yl)-3- [(2R)-1-methyl pyrrolidine- 2-yl] acrylamide; and 5, preparing the pyrrotinib. The method has the advantages of easily available raw materials, simple process, economy, environmental protection, and facilitation of improvement and control of the quality of final product bulkdrugs.

Preparation process of pyrotinib

The invention discloses a preparation process of pyrotinib, and belongs to the technical field of chemical synthesis of medicines. According to the method, (2E)-N-(4-amino-3-cyano-7-ethoxyquinolin-6-yl)-3-[(2R)-1-methylpyrrolidin-2-yl]acrylamide as shown in a formula I and 2-[(2-chloro-4-methylthiophenoxy)methyl]pyridine as shown in a formula II undergo a substitution reaction in a solvent under the action of a base catalyst to obtain pyrotinib. The preparation method has the characteristics of easily available raw materials, simple process, economy, environmental protection and the like, is beneficial to quality control and improvement of final product bulk drugs, and can meet the requirements of industrial production.

Synthesis method of pyrotinib

The invention discloses a synthesis method of pyrotinib, which belongs to the technical field of chemical synthesis of medicines. The preparation method comprises the following steps of firstly, reacting 2-[(4-bromo-2-chlorophenoxy)methyl]pyridine with n-butyllithium at a low temperature, and then carrying out a boronation reaction with an organic boron reagent to obtain [3-chloro-4-(pyridine-2-ylmethoxy)phenyl]boric acid, enabling (2E)-N-(4-amino-3-cyano-7-ethoxy quinoline-6-yl)-3-[(2R)-1-methyl pyrrolidine-2-yl] acrylamide and the obtained [3-chloro-4-(pyridine-2-yl methoxy)phenyl]boric acid to be subjected to a catalytic coupling reaction in a system of a copper catalyst, a base catalyst and a solvent, and acquiring pyrotinib. The method has the characteristics of readily available rawmaterials, simple process, economy, environmental protection and the like, is beneficial to quality control and improvement of final product raw material medicines, is suitable for industrial production and is beneficial to promoting cheap development of the raw material medicines.

METHOD FOR PREPARING TYROSINE KINASE INHIBITOR AND DERIVATIVE THEREOF

The present invention relates to a method for preparing a tyrosine kinase inhibitor and a derivative thereof. The present method has a short synthesis route, low costs, easy operation, and is suitable for large-scale production.

Compound (E)-3-(1-methylpyrrolidine-2-yl)-acrylic hydrochloride and synthetic method

The invention discloses a compound (E)-3-(1-methylpyrrolidine-2-yl)-acrylic hydrochloride and a synthetic method. The compound is structurally as shown in a formula (I). The synthetic method of the compound comprises the following steps: using BOC-L-prolinol (or BOC-D-prolinol) as an initial material, and by oxidization, forming aldehyde; removing a BOC protective agent; then reacting with haloalkane; then by a Wittig reaction, synthesizing (S,E)-3-(1-methylpyrrolidine-2-yl)-ethyl acrylate; after hydrolysis, salifying to obtain (S,E)-3-(1-methylpyrrolidine-2-yl)-acrylic hydrochloride [or (R,E)-3-(1-methylpyrrolidine-2-yl)-acrylic hydrochloride]. The compound, as a medical intermediate, can be used for preparing quinazoline or quinolines medicine derivatives. The formula is shown in the description.

6-AMINO QUINAZOLINE OR 3-CYANO QUINOLINE DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF

The present disclosure relates to 6-amino quinazoline or 3-cyano quinoline derivatives, preparation processes and pharmaceutical compositions containing them. Specifically, the present disclosure relates to novel 6-amino quinazoline or 3-cyano quinoline derivatives presented by formula (I), or its tautomer, enantiomer, diastereomer, racemate or pharmaceutically acceptable salts thereof, or metabolite, metabolic precursor or prodrug thereof, and the uses for treatment especially for protein kinase inhibitors, in which each substitute group of general formula (I) is as defined in the specification.

4-quinazoline amine derivatives and their use

A 4-quinazoline amine derivative as represented by formula (1), a pharmaceutical composition comprising the derivative, and an application thereof in preparing medicine for curing cancer. The cancer is a drug-resistant cancer, preferably a cancer resisting an EGFR reversible inhibitor, and more preferably, a cancer resisting gefitinib, erlotinib or lapatinib; alternatively, the cancer carries EGFR mutation.

PHARMACEUTICALLY ACCEPTABLE SALT OF (E)-N-[4-[[3-CHLORO-4-(2-PYRIDYLMETHOXY)PHENYL]AMINO]-3-CYANO-7-ETHOXY-6-QUINOLYL]-3-[(2R)-1-METHYLPYRROLIDIN-2-YL]PROP-2-ENAMIDE, PREPARATION METHOD THEREFOR, AND MEDICAL USE THEREOF

Provided as represented by formula (I) is a pharmaceutically acceptable salt of (E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl] -3-[(2R)-1-methylpyrrolidin-2-yl]prop-2-enamide, a preparation method therefor, and a use thereof as a therapeutic agent and especially as a protein kinase inhibitor.

PHARMACEUTICALLY ACCEPTABLE SALT OF (E)-N-[4-[[3-CHLORO-4-(2-PYRIDYLMETHOXY)PHENYL]AMINO]-3-CYANO-7-ETHOXY-6-QUINOLYL]-3-[(2R)-1-METHYLPYRROLIDIN-2-YL]PROP-2-ENAMIDE, PREPARATION METHOD THEREOF, AND MEDICAL USE THEREOF

Provided as represented by formula (I) is a pharmaceutically acceptable salt of (E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-3-[(2R)-1-methylpyrrolidin-2-yl]prop-2-enamide, a preparation method thereof, and a use thereof as a therapeutic agent, and especially as a protein kinase inhibitor.

6-AMINO QUINAZOLINE OR 3-CYANO QUINOLINE DERIVATIVES, PREPARATION METHODS AND PHARMACEUTICAL USES THEREOF

6-amino quinazoline or 3-cyano quinoline derivatives, preparation methods and pharmaceutical uses thereof are disclosed. Specifically, the present disclosure discloses novel 6-amino quinazoline or 3-cyano quinoline derivatives presented by general formula (I), or tautomers, enantiomers, diastereomers, racemates or pharmaceutically acceptable salts thereof, or metabolites, metabolic precursors or prodrugs thereof, and their uses as treatment agents especially as protein kinase inhibitors, in which each substitutent group of general formula (I) is as defined in the specification.