Top Picks: new discover of (S)-1-Phenyl-1,2,3,4-tetrahydroisoquinoline

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Asymmetric transfer hydrogenation of 1-phenyl dihydroisoquinolines using Ru(II) diamine catalysts

A new [Ru(II)(eta6-p-cymene)(1R,2R)-N-((1S,2S)-borneol-10- sulfonyl)-1,2-diphenylethylenediamine] catalyst for the asymmetric transfer hydrogenation of both 1-alkyl and 1-aryl dihydroisoquinolines has been isolated. For the first time in this type of reaction, the catalyst employs an N-alkylsulfonyl group instead of N-arylsulfonyl.

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

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PROCESS FOR PREPARATION OF ENANTIOMERICALLY PURE (S)-1-PHENYI-1,2,3,4- TETRAHYDROISOQUINOLINE

Process for preparation of (S)-1 -phenyl-1, 2,3, 4-tetrahydroisoquinoline is characterized in that 1-phenyl-1,2,3, 4-tetrahydroisoquinoline is reacted with D-(-)- tartaric acid in a solvent system consisting of methanol and water, preferably at 3.3:1 to 1 :1 volume ratio, the crystallization mixture is left for crystallization and (S)-1-phenyl-1,2,3, 4-tetrahydroisoquinoline is released from obtained crystalline diastereoisomeric salt according to standard procedures. (S)-1-Phenyl- 1,2,3, 4-tetrahydroisoquinoline is the intermediate in enantiomeric synthesis of solifenacin.

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

Properties and Exciting Facts About (S)-1-Phenyl-1,2,3,4-tetrahydroisoquinoline

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Asymmetric Transfer Hydrogenation of 1-Aryl-3,4-Dihydroisoquinolines Using a Cp*Ir(TsDPEN) Complex

We report herein a simple alternative method for the asymmetric transfer hydrogenation (ATH) of 1-aryl-3,4-dihydroisoquinolines (1-Ar-DHIQs) that are known to be challenging substrates owing to their poor reactivity. The hydrogenation protocol employs the readily available Cp*Ir(TsDPEN) {where Cp* = pentamethylcyclopentadienyl and TsDPEN = (S,S)-HNCHPhCHPhNTs2?} catalytic complex, 2-propanol and HCOOH/triethylamine mixture as the solvent and hydrogen donor, and anhydrous phosphoric acid as an inexpensive additive. The series of examined substrates shows a favorable tolerance to various functional groups. Unlike 1-alkyl-DHIQs, where the enantiomeric excess (ee) starkly changes during the course of hydrogenation, 1-Ar-DHIQs exhibit a constant ee value, which makes the method practical and useful for the production of fine chemicals containing the 1,2,3,4-tetrahydroisoquinoline motif.

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

Extracurricular laboratory:new discovery of (S)-1-Phenyl-1,2,3,4-tetrahydroisoquinoline

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Discovery of a 1-isopropyltetrahydroisoquinoline derivative as an orally active N-type calcium channel blocker for neuropathic pain

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

Some scientific research about (S)-1-Phenyl-1,2,3,4-tetrahydroisoquinoline

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Concise Redox Deracemization of Secondary and Tertiary Amines with a Tetrahydroisoquinoline Core via a Nonenzymatic Process

A concise deracemization of racemic secondary and tertiary amines with a tetrahydroisoquinoline core has been successfully realized by orchestrating a redox process consisted of N-bromosuccinimide oxidation and iridum-catalyzed asymmetric hydrogenation. This compatible redox combination enables one-pot, single-operation deracemization to generate chiral 1-substituted 1,2,3,4-tetrahydroisoquinolines with up to 98% ee in 93% yield, offering a simple and scalable synthetic technique for chiral amines directly from racemic starting materials.

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

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Ferritin encapsulation of artificial metalloenzymes: Engineering a tertiary coordination sphere for an artificial transfer hydrogenase

Ferritin, a naturally occuring iron-storage protein, plays an important role in nanoengineering and biomedical applications. Upon iron removal, apoferritin was shown to allow the encapsulation of an artificial transfer hydrogenase (ATHase) based on the streptavidin-biotin technology. The third coordination sphere, provided by ferritin, significantly influences the catalytic activity of an ATHase for the reduction of cyclic imines.

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

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Synthesis of 1,1-disubstituted tetrahydroisoquinolines by lithiation and substitution, with in situ IR spectroscopy and configurational stability studies

Lithiation of N-Boc-1-phenyltetrahydroisoquinolines was optimized by in situ IR spectroscopy. The kinetics for rotation of the carbamate group and for the enantiomerization of the organolithium were determined. The organolithium is configurationally stable at low temperature, and the asymmetric synthesis of 1,1-disubstituted tetrahydroisoquinolines can be achieved with high yields and high enantiomer ratios. The chemistry was applied to the preparation of FR115427 and provides a way to recycle the undesired enantiomer in the synthesis of solifenacin.

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

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Dual Stereocontrol for Enantioselective Hydrogenation of Dihydroisoquinolines Induced by Tuning the Amount of N-Bromosuccinimide

An efficient dual stereocontrol in iridium-catalyzed hydrogenation of 1-substituted 3,4-dihydroisoquinolines was realized by tuning the amount of N-bromosuccinimide using chiral ligand of single configuration, providing both enantiomers of 1-substituted 1,2,3,4-tetrahydroisoquinolines with up to 89% ee (S) and 98% ee (R), respectively. Dual activation role of N-bromosuccinimide is proposed to be responsible for the reversal of enantioselectivity under two hydrogenation conditions.

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

Discovery of (S)-1-Phenyl-1,2,3,4-tetrahydroisoquinoline

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A NEW METHOD FOR THE PREPARATION OF SOLIFENACIN AND NEW INTERMEDIATE THEREOF

A new method for the preparation of solifenacin by reacting quinuclidin-3-ol and bis (aryl) carbonate to form (3R)-l -azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate of formula (IVa); and treating (3R)-I – azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate of formula (IVa) with (1S)- I -phenyl- 1, 2, 3, 4- tetrahydroisoquinoline in an inert atmosphere to form a Solifenacin base which is converted into its pharmaceutically acceptable salts. The invention also provide new compound, (3R)-1 – azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate, which is used as an intermediate for the preparation of Solifenacin base and a process for the preparation thereof.

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

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The role of the aromatic ligand in the asymmetric transfer hydrogenation of the CN bond on Noyori’s chiral Ru catalysts

Only four types of dimeric precursors [RuCl2(eta6-arene)]2 for the synthesis of Noyori’s half sandwich diamine catalysts [RuCl(TsDPEN)(eta6-arene)] are commercially available, yet so far no study has tried to systematically evaluate how these systems perform during the asymmetric transfer hydrogenation of various 3,4-dihydroisoquinolines (i.e., the typical substrates for Noyori asymmetric transfer hydrogenation benchmarking). Experiments combined with molecular modeling allowed us to assess their properties and formulate a hypothesis clarifying the difference in enantioselectivity of these systems.

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