1-Azabicyclo[2.2.2]octan-3-yl (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate;butanedioic acid

Base Information

• Chemical Name: 1-Azabicyclo[2.2.2]octan-3-yl (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate;butanedioic acid
• CAS No.: 242478-38-2
• Molecular Formula: C₄H₆O₄*C₂₃H₂₆N₂O₂
• Molecular Weight: 480.561
• Hs Code.: 29339900
• European Community (EC) Number: 620-505-5
• NCI Thesaurus Code: C73805
• RXCUI: 476588
• Mol file: 242478-38-2.mol

Synonyms:2(1H)-Isoquinolinecarboxylic acid, 3,4-dihydro-1-phenyl-,1- azabicyclo(2.2.2)oct-3-yl ester, (R-(R*,S*))-;905, YM;quinuclidin-3'-yl-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate;solifenacin;solifenacin succinate;Succinate, Solifenacin;vesicare;YM 905;YM905

Chemical Property of 1-Azabicyclo[2.2.2]octan-3-yl (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate;butanedioic acid

Chemical Property:

• Vapor Pressure: 2.41E-10mmHg at 25°C
• Melting Point: ~145°
• Refractive Index: 1.648
• Boiling Point: 505.5 °C at 760 mmHg
• Flash Point: 259.5 °C
• PSA: 107.38000
• Density: 1.24g/cm3
• LogP: 3.67650
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility.: Methanol (Slightly, Heated, Sonicated), Water (Slightly, Sonicated)
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 6
• Exact Mass: 480.22603674
• Heavy Atom Count: 35
• Complexity: 617

Purity/Quality:

99% ^*data from raw suppliers

Solifenacin succinate ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CN2CCC1C(C2)OC(=O)N3CCC4=CC=CC=C4C3C5=CC=CC=C5.C(CC(=O)O)C(=O)O
• Isomeric SMILES: C1CN2CCC1C(C2)OC(=O)N3CCC4=CC=CC=C4[C@@H]3C5=CC=CC=C5.C(CC(=O)O)C(=O)O
• Recent ClinicalTrials: A Study to Evaluate the Efficacy and Safety of DA-8010 in Patients With Overactive Bladder
• Recent EU Clinical Trials: PERIPHERAL TRANSCUTANEOUS NEUROMODULATION OF THE POST-TIBIAL NERVE (T-PTNS) FOR SOLIFENACIN 10mg. IN THE TREATMENT OF HYPERACTIVE BLADDER SYNDROME: NON-INFERIORITY PHASE IV RANDOMIZED CLINICAL TRIAL
• Recent NIPH Clinical Trials: Global Assessment Study of Anti-cholinergics on Efficacy and Tolerability for Patients with OAB
• Description: Solifenacin succinate is an antimuscarinic medication that is used to treat an overactive bladder causing symptoms of frequency, urgency, or incontinence. Solifenacin is an M3 muscarinic receptor antagonist that was developed and launched for the treatment of overactive bladder (pollakiuria) in Europe. M3 receptors have been implicated in neurally evoked smooth muscle contractions of the bladder, and M2 receptors have also been suspected of playing a role because of their dominance in the detrusor muscle. Solifenacin displays affinity for both M3 and M2 receptors with Ki values of 9.9nM and 120 nM, respectively. Since muscarinic salivary glands are of the M3 persuasion, a common side effect of antimuscarinic therapy is dry mouth. At the cellular level, solifenacin possesses a selective preference for bladder over salivary gland that is 15-fold greater than that of atropine suggesting a lower probability of inducing dry mouth at pharmacologically relevant doses. The synthesis of solifenacin involves the preparation of racemic 1-phenyl- 1,2,3,4-tetrahydroisoquinoline via cyclization of N-(2-phenylethyl)benzamide, and subsequent reaction with ethyl chloroformate and transesterification with (R)- 3-quinuclidinol. Chiral chromatography affords the isolation of the desired diastereomer. Alternatively, 1-phenyl-1,2,3,4-tetrahydroisoquinoline may be subjected to optical resolution with (+)-tartaric acid prior to treatment with ethyl chloroformate and subsequent transesterification. The pooled results of four phase III trials concluded that 63% of women receiving 5mg of solifenacin once daily and 68% of women receiving 10mg once daily reported a 50% or more reduction in urgency episodes, compared to 44% of women taking placebo. This compares with a 53% reduction in patients receiving tolterodine twice daily. In another placebo-controlled trial, with the change in the number of micturitions in a 24-h period as the primary endpoint, once-daily solifenacin recorded an 18% decrease for a 5-mg dose and a 21% decrease for a 10-mg dose compared to 10% with placebo. Pharmacokinetic studies have demonstrated that solifenacin has an oral bioavailability of 90%, a long elimination half-life (50 h), low clearance (9.39 L/h), a mean Vss of 599 L, a Cmax of approximately 14 ng/mL, and a time to maximal plasma concentration of 4 h making it suitable for q.d. dosing. Furthermore, these PK parameters are not affected by food ingestion. Solifenacin is excreted predominantly in the feces with only 3–6% found in urine. It is contraindicated in patients with hepatic impairment, gastric retention, urinary retention, or uncontrolled narrow angle glaucoma. Further precautions, such as dose adjustment, should be considered for patients with concurrent use of ketoconazole or other potent CYP3A4 inhibitors or for patients with a history of QT prolongation or currently on medications known to prolong the QT interval. Finally, while other muscarinic antagonists have been explored in the treatment of irritable bowel syndrome (IBS), it is too early to predict the therapeutic utility of solifenacin for IBS although animal studies are promising.
• Uses: Muscarinic M3 receptor antagoinst. Used in treatment of urinary incontinence. Solifenacin succinate is a urinary antispasmodic of the antimuscarinic class.
• Clinical Use: Selective M3 antimuscarinic Symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency
• Drug interactions: Potentially hazardous interactions with other drugs Avoid if GFR<30 mL/min if also taking itraconazole, ketoconazole or ritonavir. Anti-arrhythmics: increased risk of antimuscarinic side effects with disopyramide.

Technology Process of 1-Azabicyclo[2.2.2]octan-3-yl (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate;butanedioic acid

There total 43 articles about 1-Azabicyclo[2.2.2]octan-3-yl (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate;butanedioic acid which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 100.0%

succinic acid (110-15-6) + solifenacin (242478-37-1,180272-14-4) → solifenacin succinate (1262506-09-1,242478-38-2)

Guidance literature:

In toluene; at 20 - 50 ℃; Product distribution / selectivity;

Reference yield: 89.0%

succinic acid (110-15-6) + solifenacin (242478-37-1,180272-14-4) → (1S)-(3R)-1-azabicyclo[2.2.2]oct-3-yl 3,4-dihydro-1-phenyl-2(1H)-isoquinoline carboxylate succinate (1262506-09-1,242478-38-2)

Guidance literature:

In isopropyl alcohol; at 20 ℃;

Reference yield: 89.0%

(1S)-3,4-dihydro-1-phenyl-2-(1H)-isoquinolinecarboxylic acid (3S)-1-azabicyclo[2.2.2]oct-3-yl ester (732228-02-3,180272-14-4) + (3R)-1-azabicyclo[2.2.2]oct-3-yl (1R)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylate (740780-79-4,180272-14-4) + succinic acid (110-15-6) + (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (22990-19-8,96719-89-0,118864-75-8) + solifenacin (242478-37-1,180272-14-4) → (1S)-3,4-dihydro-1-phenyl-2-(1H)-isoquinolinecarboxylic acid (3S)-1-azabicyclo[2.2.2]oct-3-yl ester succinate (862207-71-4,1262506-09-1,242478-38-2) + (3R)-1-azabicyclo[2.2.2]oct-3-yl (1R)-3,4-dihydro-1-phenyl-2(1H)-isoquinoline carboxylate succinate (862207-70-3,1262506-09-1,242478-38-2) + 1-(S)-phenyl-1,2,3,4-tetrahydroisoquinoline succinate + solifenacin succinate (1262506-09-1,242478-38-2)

Guidance literature:

In isopropyl alcohol; at 20 ℃;

upstream raw materials:

succinic acid

solifenacin

(1S)-3,4-dihydro-1-phenyl-2-(1H)-isoquinolinecarboxylic acid (3S)-1-azabicyclo[2.2.2]oct-3-yl ester

(3R)-1-azabicyclo[2.2.2]oct-3-yl (1R)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylate

Refernces

• 1、 -. "A succinic acid thorley that new preparation method". Paragraph 0018; 0037-0039. . Retrieved 2017/09/19.
• 2、 -. "After-treatment for solifenacin and method for preparing succinic acid solifenacin". Paragraph 0062; 0063. . Retrieved 2016/12/01.