85175-59-3

Basic information

• Product Name: (Z)-3-(3-chloropropyl)-7,8-diethyl-1H-benzo[d] azepin-2 (3H)-one
• Synonyms: (Z)-3-(3-chloropropyl)-7,8-diethyl-1H-benzo[d] azepin-2 (3H)-one;,8-Dimethoxy-3-(3-chloropropyl)-1,3-dihydro-2H-3-benzazepin-2-one;3-(3-Chloropropyl)-1,3-dihydro-7,8-dimethoxy-2H-3-benzazepin-2-one;7,8-Dimethoxy-3-(3-chloropropyl)-1,3-dihydro-2H-3-benzazepin-2-one;3-(3-Chloro-propyl)-7,8-dimethoxy-1,3-dihydro-benzo[d]azepin-2-one;3-(3-chloropropyl)-7,8-diMethoxy-2,3-dihydro-1H-3-benzazepin-2-one;3-(3-Chloropropyl)-7,8-diMethoxy-1H-3-benzazepin-2(3H)-one;2H-3-Benzazepin-2-one, 3-(3-chloropropyl)-1,3-dihydro-7,8-diMethoxy-
• CAS NO: 85175-59-3
• Molecular Formula: C₁₅H₁₈ClNO₃
• Molecular Weight: 295.76
• EINECS: 1592732-453-0
• Mol File: 85175-59-3.mol

Chemical Properties

• Melting Point: 100-102 °C(Solv: ethanol (64-17-5))
• Boiling Point: 484.1 °C at 760 mmHg
• Flash Point: 246.6 °C
• Appearance: /
• Density: 1.191 g/cm³
• Vapor Pressure: 1.58E-09mmHg at 25°C
• Refractive Index: 1.544
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: -1.23±0.20(Predicted)
• CAS DataBase Reference: (Z)-3-(3-chloropropyl)-7,8-diethyl-1H-benzo[d] azepin-2 (3H)-one(CAS DataBase Reference)
• NIST Chemistry Reference: (Z)-3-(3-chloropropyl)-7,8-diethyl-1H-benzo[d] azepin-2 (3H)-one(85175-59-3)
• EPA Substance Registry System: (Z)-3-(3-chloropropyl)-7,8-diethyl-1H-benzo[d] azepin-2 (3H)-one(85175-59-3)

Safety Data

• Hazardous Substances Data: 85175-59-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(Z)-3-(3-chloropropyl)-7,8-diethyl-1H-benzo[d] azepin-2 (3H)-one is used as a pharmaceutical intermediate for the synthesis of ivabradine hydrochloride and its medicinal salts, which possess important therapeutic properties in managing heart rate and treating myocardial ischemia conditions.
Used in Synthesis of Zatebradine Analogues:
(Z)-3-(3-chloropropyl)-7,8-diethyl-1H-benzo[d] azepin-2 (3H)-one is used as a reactant in the synthesis of Zatebradine analogues, which are potential blockers of hyperpolarization-activated current, indicating its utility in developing new compounds with potential therapeutic applications.

synthetic

1.5g (6.8mmol) of 7,8-dimethoxy-1,3-dihydro-2h-3-benzoaza-2-one, 1.5g (9.5mmol) of 1,3-bromochloropropane and 6ml of DMF into a flask, raise the temperature of the mixture to 40 ℃, and add 0.8g of 40% sodium hydroxide (8mmol) solution. The mixture was then heated to 60 ° C and stirred for 2 hours; Add 30 ml of ice water and stir for 1 hour under the cooling of ice water bath. Filter out solid precipitates, wash and dry. The yield of the title compound was 85%.

InChI:InChI=1/C15H18ClNO3/c1-19-13-8-11-4-7-17(6-3-5-16)15(18)10-12(11)9-14(13)20-2/h4,7-9H,3,5-6,10H2,1-2H3

Upstream product

• 73942-87-7 7,8-Dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one 
• 109-70-6 1.3-chlorobromopropane 
• 93-40-3 (3,4-Dimethoxyphenyl)acetic acid 
• 73954-34-4 N-(2,2-dimethoxy-ethyl)-3,4-dimethoxyphenylacetamide 
• 10313-60-7 3,4-dimethoxyphenylacetyl chloride 
• 865-47-4 potassium tert-butylate 
• 5663-56-9 2-(3,4-dimethoxyphenyl)acetamide 
• 93-17-4 3,4-dimethoxyphenylacetonitrile 

Downstream Products

• 85176-36-9 7,8-Dimethoxy-3-(3-{methyl-[2-(4-nitro-phenyl)-ethyl]-amino}-propyl)-1,3-dihydro-benzo[d]azepin-2-one 
• 92460-24-7 1-[7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-on-3-yl]-3-[N-methyl-N-(5-{3,4-dimethoxy-phenyl}-pentyl)-amino]-propane 
• 374538-56-4 3-{3-[2-(3,4-Dimethoxy-phenyl)-ethylamino]-propyl}-7,8-dimethoxy-1,3-dihydro-benzo[d]azepin-2-one 

Relevant articles and documents

AN IMPROVED PROCESS FOR THE SYNTHESIS OF IVABRADINE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS

: Disclosed herein is an improved process for the preparation of Ivabradine and pharmaceutically acceptable salts thereof. The invention more particularly disclosesthe synthesis of key intermediates viz.,(S)-N-[(4,5-dimethoxybenzocydobut-l-yl)-methyl]-N- (methyl)amine hydrochloride of Formula-II and 3-(3-Iodopropyl)-7,8-dimethoxy-1,3-dihydro-2H-3-benzapin-2-one of Formula-III, and its use in industrial synthesis of Ivabradine and pharmaceutically acceptable salts thereof.

Synthetic method of ivabradine

The invention provides a synthetic method of ivabradine. The synthetic method of ivabradine comprises following steps: 1, a compound II and bromo chloropropane are subjected to alkylation reaction under the catalytic effect of a first alkali so as to obtain a compound III; 2, the compound III is subjected to hydrogenation reaction in a palladium on carbon and ammonium formate system so as to obtain a compound IV; 3, the compound IV and an iodination reagent are subjected to iodization reaction so as to obtain a compound V; 4, the compound V and the compound VI are subjected to condensation reaction under the catalytic effect of a second alkali so as to obtain a compound I. Operation is simple; reaction conditions are mild; the raw materials are commercially available; the synthetic methodis simple; cost is low; and the ivabradine synthesis difficulty is reduced greatly.

PROCESS FOR THE PREPARATION OF BENZAZEPINE-2-ONE DERIVATIVE

The present, invention relates to a cost effective, environment friendly industrially viable process for the preparation of 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepine-2-one, an intermediate used in the preparation of ivabradine, without using acid chloride intermediate and condensing agent.

PROCESS FOR PREPARATION OF IVABRADINE

A process for the preparation of ivabradine pharmaceutically acceptable salts is disclosed. An amorphous form of ivabradine hydrochloride and a process for the preparation of it are also provided.

IVABRADINE HYDROCHLORIDE AND THE PROCESSES FOR PREPARATION THEREOF

The present disclosure relates to a process of preparing Ivabradine Hydrochloride, which is devoid of product related impurities. More specifically, the present disclosure provides a process to obtain a new polymorph of Ivabradine Hydrochloride, wherein said polymorph is pure and devoid of impurities at particular RRTs. The disclosure further relates to the removal of specific impurities of Formula 8 and/or Formula 9 during the preparation of said Ivabradine Hydrochloride. The disclosure also specifically provides the said polymorphic form of Ivabradine Hydrochloride.

Synthesis and biological activity of some 1,3-dihydro-2H-3-benzazepin-2- ones with a piperazine moiety as bradycardic agents

A series of 1,3-dihydro-2H-3-benzazepin-2-ones with a piperazine moiety were designed and synthesized by treating the common intermediate of 1,3-dihydro-7,8-dimethoxy-3-[3-(1-piperazinyl)-propyl]-2H-3-benzazepin-2-ones with a variety of N-aryl-2-chloroacetamides and acyl chlorides. Their structures have been characterized by 1H-NMR, MS, and elemental analysis. The title compounds were evaluated for their bradycardic activity in vitro. Most of the synthesized compounds exhibited some vasorelaxant activity and heart-rate-reducing activity with bradycardic potency.

PROCESS FOR PREPARATION OF IVABRADINE

The present invention describes a new process for optical resolution of [N-[[3,4- dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl]-N-methylamine] which is an intermediate in the preparation of ivabradine.

(Benzocycloalkyl) alkylamines

The compounds are 3-[ (benzocycloalkyl)alkyl amino alkyl] -1,3,4,5-te trahydro 2H- 3-benzazepin-2 ones useful in cardiovascular field.A compound disclosed is (R,S)-7,8-dimethoxy-3-{3-{N-[(4,5-dimethoxybenzocyclobut-1-yl) methyl]-N-methyl amino}propyl}-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one.

Specific bradycardic agents. 1. Chemistry, pharmacology, and structure-activity relationships of substituted benzazepinones, a new class of compounds exerting antiischemic properties

Structural modification of the calcium-antagonist verapamil (1) by replacement of the lipophilic α-isopropylacetonitrile moiety by various heterocyclic ring systems has led to a new class of cardiovascular compounds which are characterized by a specific bradycardic activity. These agents reduce heart rate without binding to classical calcium channels or β-adrenoceptors, interacting instead specifically with structures at the sino atrial node. Therefore they have also been termed sinus node inhibition. The prototype falipamil (2) has been submitted to furthr optimization mainly hy manipulation of the phthalimidine moiety. This has resultd in a secod generation of specific bradycardic agents with increased potency and selectively and prolonged duration of action represented by the benzazepinone-derivative UL-FS 49 (4). Structure-activity relationships within this novel class of compounds have revealed a marked dependence of activity on the substitution pattern of the aromatic rings, the nature of the central nitrogen atom, and the length of the connecting alkyl chains. The crucial role of the benzazepione ring for bradycardic activity can be best explained by its special impact on the overall molecular conformation.

(2H)-3-benzazepin-2-ones, their pharmaceutical compositions and their pharmaceutical uses

The invention relates to new heteroaromatic amine derivatives of formula STR1 wherein A represents a --CH2 --CH2 --, --CH=CH--or STR2 group and B represents a methylene, carbonyl or thiocarbonyl group or A represents a --CO--CO or STR3 group and B represents a methylene group, in which the carbon atom marked x is linked to the phenyl nucleus, E represents a straight-chained alkylene group optionally substituted by an alkyl group, G represents a straight-chained alkylene group optionally substituted by an alkyl group, R1 represents a hydrogen, fluorine, chlorine or bromine atom, a trifluoromethyl, nitro, amino, alkylamino, dialkylamino, alkyl, alkylmercapto, hydroxy, alkoxy or phenylalkoxy group, R2 represents a hydrogen, chlorine or bromine atom or a hydroxy, alkoxy, phenylalkoxy or alkyl group or R1 and R2 together represent an alkylenedioxy group, R3 represents a hydrogen atom, an alkenyl group, an alkyl or phenylalkyl group, and Het represents a 5- or 6-membered heteroaromtic ring bonded via a carbon or nitrogen atom, which contains an oxygen, sulphur or nitrogen atom, two nitrogen atoms or a nitrogen atom and an oxygen or sulphur atom, and onto which additionally a phenyl ring can be condensed, in which case the bond can also be via the phenyl nucleus, or an imidazo[1,2-a]pyridyl group wherein the carbon structure of the above-mentioned groups can be substituted by a methylenedioxy or ethylenedioxy group or can be mono- or disubstituted by a halogen atom or an alkyl, hydroxy, alkoxy, phenylalkoxy, phenyl, dimethoxyphenyl, nitro, amino, acetylamino, carbamoylamino, N-alkyl-carbamoylamino, hydroxymethyl, mercapto, alkylmercapto, alkylsulphinyl, alkylsulphonyl, alkylsulphonyloxy, alkylsulphonylamino, alkoxycarbonylmethoxy, carboxymethoxy or alkoxymethyl group, and at the same time any imino group present in the above-mentioned heteroaromatic groups can be substituted by an alkyl, phenylalkyl or phenyl group, the N-oxides and the acid addition salts thereof with inorganic or organic acids, which have valuable pharmacological properties, particularly the effect of lowering heart rate and oxygen requirement of the heart. They can be used to treat sinus tachycardia or ischaemic heart disease.