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Disclosed herein is a method of preparing solifenacin or a salt thereof, including the steps of: (a) reacting (R)-quinuclidinol with bis(pentafluorophenyl)carbonate in an organic solvent to prepare a solifenacin intermediate,(3R)-1-azabicyclo[2,2,2]oct-3-yl pentafluorophenylcarbonate, and (b) reacting the solifenacin intermediate with (1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline in an organic solvent to prepare solifenacin. The method is advantageous in that high-purity solifenacin or a salt thereof can be simply and efficiently prepared with high yield using a novel intermediate.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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An efficient procedure for the asymmetric synthesis of 1-substituted1,2,3,4-tetrahydro-9-methyl-beta-carbolines based on asymmetric electrophilic alpha-amidoalkylation reactions is described. Stereoselective addition of various organometallic reagents to a chiral N-acyl-beta-carbolinium ion gave the corresponding 1-substituted 1,2-dihydro-beta-carbolines in high yields and very good to excellent diastereomeric ratios. Catalytic hydrogenation followed by the removal of the chiral auxiliary via reductive cleavage of the amide bond proceeded with complete conservation of the absolute configuration at the newly created stereocenter leading to 1-substituted 1,2,3,4-tetrahydro-9-methyl-beta-carboline derivatives in high yields. Their absolute stereochemistry was proven by X-Ray analysis. The 1-phenyl-substituted 1,2,3,4-tetrahydro-beta-carbolines were evaluated for their affinity to the PCP binding site of the NMDA receptor.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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The invention belongs to the field of medicine, in particular relates to a new process for the preparation of intermediates thorley that. The 2-halo benzophenoneoxime protection of the carbonyl group, n-butyl aldehyde after the lithium pulls out the bromine on, then with nitro methane condensation, catalytic hydrogenation reduction postacidification, then loop, passes through the reduction, chiral resolution alkaline hydrolysis after the new intermediate compounds by thorley I; the new intermediate thorley that the structural formula is: The invention utilizes the simple and easily obtained starting material, the production cost is reduced. This process route is advanced, mild reaction conditions, the reaction yield is high, little three waste, no expensive and toxic reagent, reaction solvent distillation can be applied mechanically, easy commercial production, has great social and economical benefits of environmental protection. (by machine translation)

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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N-type calcium channel blockade is a promising therapeutic approach for the treatment of neuropathic pain. Starting from lead compound (S)-1, we focused our optimization efforts on potency for N-type calcium channel inhibition and improvement of CYP inhibition profile. 2-{[(1-Hydroxycyclohexyl)methyl]amino}-(1R)-(1-isopropyl-6-methoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethanone oxalate ((R)-5r) was identified as a novel orally active small-molecule N-type calcium channel inhibitor with reduced CYP inhibition liability. Oral administration of (R)-5r improved mechanical allodynia in a spinal nerve ligation model of neuropathic pain in rats with an ED50 value of 2.5 mg/kg.

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1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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S(-)1-Phenyl-1,2,3,4-tetrahydro isoquinoline acetamide analogues are prepared by sequence of reactions which involve a metal hydride reduction of 3,4-dihydroisoquinoline followed by separation of S-form with mandelic acid (chiral reagent) by resolution. The product S(-)1-phenyl-1,2,3,4-tetrahydro isoquinoline is treated with halosubstituted acetyl chlorides to obtain tetrahydro isoquinoline acetyl chloride which is further employed to synthesize acetamide derivatives of tetrahydro isoquinoline using various substituted aryl amines. The products were characterized by advanced spectroscopic techniques.

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Compositions and/or formulations comprising solifenacin or a salt thereof and processes for preparing the same. Certain compositions and formulations contain a stable amorphous form of solifenacin succinate.

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The present invention relates to a process for the preparation of Solifenacin succinate by condensing a compound of formula (IVb) with (RS)-3-quinuclidinol, wherein, R represents methyl, ethyl, isopropyl; to produce a diastereomeric mixture of (1S)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylic acid (3RS)-1-azabicyclo[2.2.2]oct-3-yl ester, which is treated with succinic acid in a solvent or mixture of solvents to produce optically pure Solifenacin succinate, Formula (X).

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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Asymmetric hydrogenation of 1-aryl-3,4-dihydroisoquinolines using the [IrCODCl]2/(R)-3,5-diMe-Synphos catalyst is reported. Under mild reaction conditions, this atom-economical process provides easy access to a variety of enantioenriched 1-aryl-1,2,3,4-tetrahydroisoquinoline derivatives, which are important pharmacophores found in several pharmaceutical drug candidates, in high yields and enantiomeric excesses up to 99% after a single crystallization.

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A series of (S)-N-substitued-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxamide derivatives were designed, synthesized and evaluated for their anti-inflammatory and analgesic effects in vivo. Among the synthesized compounds 2a and 2n showed the best anti-inflammatory activity (inhibition rate: 95% and 92.7%, respectively) and analgesic effect (inhibition rate: 100% and 100%, respectively), which was greater than that or nearly equivalent to that of indomethacin. Compounds 2a and 2n were selected to test their inhibitory effects against ovine COX-1 and COX-2 using the cyclooxygenase inhibition assay in vitro. Compounds 2a and 2n are weak inhibitors of COX-1 isozyme but displayed moderate COX-2 isozyme inhibitory effects (IC50 = 0.47 muM and 1.63 muM, respectively) and COX-2 selectivity indexes (SI = 11.5 and 4.8). Furthermore, compound 2a was more inhibitors of COX-2 isozyme active than the reference drug celecoxib.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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The invention discloses a preparation method of a chiral amine compound. In presence of a semi-sandwich type complex and an acid additive, an asymmetrization reaction is carried out on a prochiral amine compound in a hydrogen atmosphere, and postprocessing is carried out after the reaction is completely finished, so that the chiral amine compound is obtained. According to the preparation method of the chiral amine compound, a certain amount of appropriate acid is added in a certain sequence, so that activation of a C=N bond in a reduction reaction can be promoted; the prepared chiral amine compound can be taken as an intermediate and used for synthesizing the following medicines (including but not limited to the medicines) or precursors of the medicines: gantacurium, mivacurium chloride, atracurium besylate, sertraline, sezolamide, almorexant or solifenacin.

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Reference:
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem