144481-98-1

Basic information

• Product Name: Benzenepropanoic acid,4-[(2S)-2-hydroxy-3-[[2-[(4-morpholinylcarbonyl)amino]ethyl]amino]propoxy]-,[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl ester, hydrochloride (1:1)
• Synonyms: Benzenepropanoicacid,4-[(2S)-2-hydroxy-3-[[2-[(4-morpholinylcarbonyl)amino]ethyl]amino]propoxy]-,[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl ester, monohydrochloride (9CI);Benzenepropanoic acid, 4-[2-hydroxy-3-[[2-[(4-morpholinylcarbonyl)amino]ethyl]amino]propoxy]-,(2,2-dimethyl-1,3-dioxolan-4-yl)methyl ester, monohydrochloride, [S-(R*,R*)]-;ONO 1101 hydrochloride;Onoact
• CAS NO: 144481-98-1
• Molecular Formula: C₂₅H₃₉N₃O₈*ClH
• Molecular Weight: 546.0534
• EINECS: 1308068-626-2
• Product Categories: APIs;API
• Mol File: 144481-98-1.mol
• Article Data: 6

Chemical Properties

• Melting Point: 125.4°
• Boiling Point: 727.5 °C at 760 mmHg
• Flash Point: 393.8 °C
• Appearance: White crystalline powder
• Density: 1.201g/cm3
• Vapor Pressure: 3.24E-22mmHg at 25°C
• Storage Temp.: Refrigerator
• Solubility: DMSO (Slightly), Ethanol (Slightly, Sonicated)
• CAS DataBase Reference: Benzenepropanoic acid,4-[(2S)-2-hydroxy-3-[[2-[(4-morpholinylcarbonyl)amino]ethyl]amino]propoxy]-,[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl ester, hydrochloride (1:1)(CAS DataBase Reference)
• NIST Chemistry Reference: Benzenepropanoic acid,4-[(2S)-2-hydroxy-3-[[2-[(4-morpholinylcarbonyl)amino]ethyl]amino]propoxy]-,[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl ester, hydrochloride (1:1)(144481-98-1)
• EPA Substance Registry System: Benzenepropanoic acid,4-[(2S)-2-hydroxy-3-[[2-[(4-morpholinylcarbonyl)amino]ethyl]amino]propoxy]-,[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl ester, hydrochloride (1:1)(144481-98-1)

Safety Data

• RTECS: DA8346700
• Hazardous Substances Data: 144481-98-1(Hazardous Substances Data)

Usage

Description

Landiolol hydrochloride (14) was launched in Japan by Ono for the treatment of intraoperative tachyarrhythmia. It improves tachyarrhythmia by selectively blocking β1 receptors located mainly in the heart and by inhibiting the action of catecholamine.

Uses

Landiolol is an ultra-short acting beta blocker that is used to treat patients with cardiac arrhythmias and is also used to treat tachycardia during anasthesia.

Synthesis

The synthesis of landiolol appeared in an earlier patent in 1990. Esterification of 3- (4-hydroxyphenyl)propionic acid (141) with 2,2-dimethyl- 1,3-dioxolan-4-ylmethyl chloride (142) in DMSO gave desired ester 143 in 57% yield. Treatment of phenol 143 with bromo epoxide 144 in the present of K2CO3 afforded ether 145 in 76% yield. Epoxide 145 was then reacted with free amine 146 via a neucleophilic ring opening process to provide landiolol (14).

InChI:InChI=1/C25H39N3O8.ClH/c1-25(2)35-18-22(36-25)17-34-23(30)8-5-19-3-6-21(7-4-19)33-16-20(29)15-26-9-10-27-24(31)28-11-13-32-14-12-28;/h3-4,6-7,20,22,26,29H,5,8-18H2,1-2H3,(H,27,31);1H/t20-,22+;/m0./s1

Upstream product

• 144256-11-1 3-(4-hydroxyphenyl)propionic acid [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl ester 
• 154467-16-0 N-(2-aminoethyl)-4-morpholine carboxamide oxalic acid 
• 144256-12-2 2,2-dimethyl-1,3-dioxolan-4S-ylmethyl 3-<4-<2(S),3-epoxypropoxy>phenyl>propionate 
• 69630-16-6 N-(2-aminoethyl)-4-morpholine carboxamide 
• 1398109-46-0 (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 3-(4-((2R)-3-chloro-2-hydroxypropoxy)phenyl)propanoate 
• 88017-03-2 2-(morpholine-4-carboxamido)ethanamino hydrochloride 
• 106-89-8 epichlorohydrin 
• 133242-30-5 2,2-dimethyl-1,3-dioxolan-4S-ylmethyl 3-<4-<3-<2-(morpholinocarbonylamino)ethylamino>-2S-hydroxypropoxy>phenyl>propionate 

Relevant articles and documents

Preparation method of landiolol hydrochloride intermediate

The invention discloses a preparation method of a high-purity landiolol hydrochloride intermediate N-(2-aminoethyl)-4-morpholinecarboxamide oxalate. The preparation method comprises the following steps: reacting N-phenoxy carbonyl morpholine with ethylenediamine, concentrating the reaction liquid, adding a solvent for dissolving, adjusting the pH value to 9-14 by using alkali, filtering to remove solid byproducts, concentrating the filtrate to obtain N-(2-aminoethyl)-4-morpholine formamide, adding water for dissolving, adjusting the pH value to 1-6 by using oxalic acid, filtering to remove a small amount of ethylenediamine oxalate solid, concentrating the filtrate, adding a solvent, and recrystallizing to obtain the high-purity N-(2-aminoethyl)-4-morpholinecarboxamide oxalate. According to the method, the high-purity landiolol hydrochloride intermediate can be obtained, the defects that the byproduct sodium phenate is difficult to filter, ethylenediamine is easy to remain and the like are overcome, the process is stable and controllable, the solvent can be recycled, and the method is more suitable for industrial production.

Method for preparing landiolol hydrochloride

The invention belongs to the field of pharmaceutical chemicals, and particularly relates to an improved method for preparing landiolol and a compound shown as a formula 8. The compound shown as the formula 8 is prepared by reacting a compound shown as a formula 7 with AH (organic amine). The invention also relates to compounds of general formula 7.

Process for the enantioselective synthesis of landiolol

PROBLEM TO BE SOLVED: To provide a process for the enantioselective synthesis of landiolol.SOLUTION: The process for the enantioselective synthesis of landiolol represented by formula (B) uses a compound represented by formula (A) as an intermediate.