118428-37-8

Basic information

• Product Name: l-Pimobendan
• Synonyms: l-Pimobendan
• CAS NO: 118428-37-8
• Molecular Formula: C₁₉H₁₈N₄O₂
• Molecular Weight: 334.377
• Mol File: 118428-37-8.mol

Chemical Properties

• Boiling Point: 471.18°C (rough estimate)
• Appearance: /
• Density: 1.2421 (rough estimate)
• Refractive Index: 1.6620 (estimate)
• PKA: 10.21±0.10(Predicted)
• CAS DataBase Reference: l-Pimobendan(CAS DataBase Reference)
• NIST Chemistry Reference: l-Pimobendan(118428-37-8)
• EPA Substance Registry System: l-Pimobendan(118428-37-8)

Safety Data

• Hazardous Substances Data: 118428-37-8(Hazardous Substances Data)

Upstream product

• 171364-79-7 2-(4-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 
• 120757-17-7 methyl 3-(4-acetaminobenzoyl)butyrate 
• 82923-97-5 3-methoxycarbonyl-2-methyl-propionic acid chloride 
• 103-84-4 Acetanilid 
• 1338058-47-1 ethyl 4-(4-(benzylamino)-3-nitrophenyl)-3-methyl-4-oxo-butanoate 
• 85633-97-2 4-(4-benzylamino-3-nitro-phenyl)-3-methyl-4-oxo-butyric acid 
• 85633-96-1 3-methyl-4-oxo-4-(3'-nitro-4'-chloro-phenyl)-butyric acid 
• 52240-25-2 4-(4-chlorophenyl)-3-methyl-4-oxobutanoic acid 
• 53012-96-7 4-(4-chlorophenyl)-3-methyl-4-oxobutyronitrile 
• 123-11-5 4-methoxy-benzaldehyde 
• 136609-85-3 6-(3,4-diaminophenyl)-5-methyl-2,3,4,5-tetrahydropyridazin-3-one 
• 117397-88-3 6-(4-chloro-3-nitrophenyl)-5-methyl-2,3,4,5-tetrahydropyridazin-3-one 
• 104-88-1 4-chlorobenzaldehyde 
• 81112-08-5 N-[4-(2-chloro-1-oxopropyl)phenyl]acetamide 

Downstream Products

• 610769-04-5 4,5-dihydro-6-(2-(4-methoxyphenyl)-1H-benzimidazol-5-yl)-5-methyl-3(2H)-pyridazinone hydrochloride 

Relevant articles and documents

Preparation method of pimobendan

The invention relates to a novel preparation process of pimobendan. Specifically, a Suzuki coupling reaction is carried out on a compound shown as a formula I (6-(2-bromo-1H-benzo[d]imidazol-6-yl)-5-methyl-4, 5-dihydropyridazin-3(2H)-one) and a compound shown as a formula II (p-methoxyphenylboronic acid or p-methoxyphenylboronic acid pinacol ester) under the action of a Pd catalyst, so that the preparation of the pimobendan is realized.

Synthesis method of pimobendan

The invention provides a synthesis method of pimobendan, and belongs to the technical field of pharmaceutical chemicals. The synthesis method comprises the following steps: (1) in an organic solvent,taking acetanilide and 2-chloropropionyl chloride as raw materials, generating a compound I under the action of a Lewis acid catalyst; (2) in acid anhydride, the compound I and nitric acid are subjected to a nitration reaction to produce a compound II; (3) carrying out nucleophilic substitution reaction on the compound II and diethyl malonate in a reaction reagent under the action of sodium methoxide, carrying out hydrolysis reaction in the reaction reagent under the action of sodium hydroxide, and regulating the pH value of the reaction system to 3-4 by using diluted hydrochloric acid to generate a compound III; (4) reacting the compound III with a decarboxylation reagent to generate a compound IV; (5) reacting the compound IV with hydrazine hydrate in a reaction solvent in the presence of a noble metal catalyst to generate a compound V; and (6) reacting the compound V with p-methoxybenzaldehyde in a reaction solvent under the action of a catalyst to generate pimobendan VI. The pimobendan prepared by the method is simple in preparation method and low in reagent toxicity and has excellent clinical curative effect and clinical safety.

Novel method for preparing pimobendan from by-product for synthesizing pimobendan

The invention discloses a novel method for preparing pimobendan from a by-product for synthesizing the pimobendan. The method comprises the following steps that the by-product (the chemical name is (5RS)-6-[1-(4-methoxybenzyl)-2-(4-methoxyphenyl)-1H-benzimidazole-6-yl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone) obtained in the pimobendan synthesizing process is dissolved into a mixed solvent and reacts with ceric ammonium nitrate (CAN) at 20-25 DEG C for 2-3 hours so as to obtain a pimobendan crude product; and the obtained pimobendan crude product is heated and refluxed in an organic solvent, and cooling, filtering and drying are carried out so as to obtain the pimobendan. According to the method, the unwanted by-product is converted into a required pimobendan product, waste is turned intowealth, and therefore the production cost is greatly lowered.

Chemical synthesis method of Pimobendan

The invention discloses a chemical synthesis method of Pimobendan. The method comprises steps as follows: acetanilide and 2-methyl-3-(chloroformyl)propionate react to produce 3-p-acetylaminobenzoyl methyl butyrate in a mixed organic solvent under the action of a composite catalyst, 3-p-acetylaminobenzoyl methyl butyrate reacts with a nitration reagent, 3-(4-acetamido-3-nitrobenzoyl)-methyl butyrate is produced and subjected to a reflux reaction with alkali in an alcohol solvent to produce 3-(4-amino-3-nitrobenzoyl) butyrate, 3-(4-amino-3-nitrobenzoyl) butyrate and hydrazine hydrate are subjected to a reflux reaction, 4,5-dihydro-5-methyl-6-(4-amino-3-nitrophenyl)-3(2H)-pyridazinone is produced and reduced with zinc powder in absolute methanol, 4,5-dihydro-5-methyl-6-(3,4-diaminophenyl)-3(2H)-pyridazinone is produced and subjected to a reflux reaction with p-anisaldehyde, and Pimobendan is obtained. The method comprises a few reaction steps, operation is safe and convenient, and the cost is low.

PIMOBENDAN MANUFACTURING PROCESS

The present invention generally relates to an improved process for the manufacture of a non- solvated crystalline compound of formula (I). The invention further relates to a new valuable intermediate compound for the commercial synthesis of pimobendan, which is a compound according to formula (I) n MeOH, wherein n is from 1 to 2 molar equivalents. Still further, the invention relates to the use of said intermediate compound or a compound according to formula (I) obtained by the process of the invention, for the manufacture of a pharmaceutical composition.

CRYSTALLINE PIMOBENDAN, PROCESS FOR THE PREPARATION THEREOF, PHARMACEUTICAL COMPOSITION AND USE

The invention relates to a pharmaceutical composition containing pimobendan as an active ingredient. The invention also relates to a crystalline form of pimobendan, as well as to a combination of said crystalline form with at least one other therapeutically active ingredient. Moreover, the invention relates to uses of said crystalline form, as well as to a pharmaceutical composition containing it. Finally, the invention relates to a process for preparing a crystalline form of pimobendan.

Substituted pyridazinones

Substituted benzylideneiminophyenylpyridazinones or dihydropyridazinones of formula I STR1 in which R1 and R8 independently mean hydrogen or lower alkyl, R2 is hydrogen, lower alkyl, trifluoromethyl, hydroxy alkyl, halogen alkyl, alkoxy alkyl, pyridyl, furyl, thienyl or cycloalkyl or one of optionally substituted groups; aryl, aralkyl, aralkenyl or nitrogen containing heterocyclic ring joining through an alkyl or alkenyl group and R3, R4 and R5 independently mean hydrogen, lower alkyl, hydroxy alkyl, halogen, hydroxy, alkoxy, acyloxy, aroyloxy, formyl, acyl, cyano, amino, carboxy or trifluoromethyl, R6 and R7 independently mean hydrogen, amino, lower alkyl, hydroxy, nitro or cyano or R2 and R7 together form a --CH2 --NH-- or --CH=N-- group and A means phenyl, naphtyl or a nitrogen containing heterocyclic ring. The compounds may be used in the treatment of congestive heart failure.