Awesome Chemistry Experiments For 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline

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SELECTIVE REMOVAL OF THE TERT-BUTOXYCARBONYL GROUP FROM SECONDARY AMINES: ZnBr2 AS THE DEPROTECTING REAGENT

ZnBr2 in dichloromethane is a convenient reagent for mild and selective removal of the tert-butoxycarbonyl group from secondary amines.

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

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Synthesis of 3-aryl-3-benzazepines: Via aryne [1,2] Stevens rearrangement of 1,2,3,4-tetrahydroisoquinolines

An efficient method for the synthesis of 3-aryl-3-benzazepines via aryne induced [1,2] Stevens rearrangement of 1,2,3,4-tetrahydroisoquinolines is described. This approach provided straightforward access to 3-aryl-3-benzazepines in moderate to good yields under transition-metal-free and strong-base-free conditions. Temperature-dependent alpha-arylated products of the carbonyl group were also obtained. Preliminary mechanistic studies suggest both 3-aryl-3-benzazepines and alpha-arylated products of the carbonyl group were generated via the rearrangement of nitrogen ylide intermediates.

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

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NHC-catalyzed Redox-Neutral Aza-Benzoin Reaction of Aldehydes with Tetrahydroisoquinolines

Tetrahydroisoquinoline derivatives are useful synthetic intermediates, which play an important role in the preparation of natural products, pharmaceuticals and other materials. Herein, we report an unprecedented redox-neutral aza-benzoin protocol to construct such scaffold. Upon exposure of tetrahydroisoquinolines to aromatic aldehydes in the presence of an NHC catalyst, the C-1 acylated tetrahydroisoquinolines were obtained in moderate to good yields.

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

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Rhodium catalyzed hydrogenation of quinolines and isoquinolines under water-gas shift conditions

Wide variety of quinolines and isoquinolines can be hydrogenated selectively in the nitrogen-containing ring by means of carbon monoxide and water in the presence of catalytic amount of rhodium carbonyl cluster. These reactions provide a useful method for the preparation of 1,2,3,4-tetrahydroquinolines and 1,2,3,4-tetrahydroisoquinolines which are key intermediates for the synthesis of isoquinoline alkaloids and other biologically active nitrogen compounds.

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

Discovery of 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline

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Bioinspired aerobic oxidation of secondary amines and nitrogen heterocycles with a bifunctional quinone catalyst

Copper amine oxidases are a family of enzymes with quinone cofactors that oxidize primary amines to aldehydes. The native mechanism proceeds via an iminoquinone intermediate that promotes high selectivity for reactions with primary amines, thereby constraining the scope of potential biomimetic synthetic applications. Here we report a novel bioinspired quinone catalyst system consisting of 1,10-phenanthroline-5,6-dione/ZnI2 that bypasses these constraints via an abiological pathway involving a hemiaminal intermediate. Efficient aerobic dehydrogenation of non-native secondary amine substrates, including pharmaceutically relevant nitrogen heterocycles, is demonstrated. The ZnI2 cocatalyst activates the quinone toward amine oxidation and provides a source of iodide, which plays an important redox-mediator role to promote aerobic catalytic turnover. These findings provide a valuable foundation for broader development of aerobic oxidation reactions employing quinone-based catalysts.

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

The important role of 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline

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Targeting P-glycoprotein: Investigation of piperine analogs for overcoming drug resistance in cancer

P-glycoprotein (P-gp) is a drug transporter that effluxes chemotherapeutic drugs and is implicated in the development of resistance of cancer cells to chemotherapeutic drugs. To date, no drug has been approved to inhibit P-gp and restore chemotherapy efficacy. Moreover, majority of the reported inhibitors have high molecular weight and complex structures, making it difficult to understand the basic structural requirement for P-gp inhibition. In this study, two structurally simple, low molecular weight piperine analogs Pip1 and Pip2 were designed and found to better interact with P-gp than piperine in silico. A one step, acid-amine coupling reaction between piperic acid and 6,7-dimethoxytetrahydroisoquinoline or 2-(3,4-dimethoxyphenyl)ethylamine afforded Pip1 and Pip2, respectively. In vitro testing in drug resistant P-gp overexpressing KB (cervical) and SW480 (colon) cancer cells showed that both analogs, when co-administered with vincristine, colchicine or paclitaxel were able to reverse the resistance. Moreover, accumulation of P-gp substrate (rhodamine 123) in the resistant cells, a result of alteration of the P-gp efflux, was also observed. These investigations suggest that the natural product analog ? Pip1 ((2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1 H)-yl)penta-2,4-dien-1-one) ? is superior to piperine and could inhibit P-gp function. Further studies are required to explore the full potential of Pip1 in treating drug resistant cancer.

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

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6,7-DIOXYALKYLTETRAHYDROISOQUINOLINE COMPOUNDS

The present invention relates to a 6,7-dioxyalkyltetrahydroisoquinoline compound, or a salt or solvate thereof according to formula I: (formula I), (I) wherein R represents hydrogen or a fluorinated alkyl group, and R2 and R3 independently represents hydrogen or an alkyl group.

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

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Nucleophilic additions to fused benzimidazole N-oxides

The benzimidazoles 16a-f have been prepared from N-oxides 15a-d. Treatment of N-oxides 15c and 15d with a mixture of acetic anhydride and sodium acetate gave the corresponding acetoxy derivatives 26 and 27 via a regiospecific nucleophilic substitution reaction. N-Oxides 15c and 15d were also deoxygenated by 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ).

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

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Arylamides hybrids of two high-affinity sigma2 receptor ligands as tools for the development of PET radiotracers

1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl] piperazine 1 (PB28) and 2-Methoxy-5-methyl-N-[4-(6,7-dimethoxy-3,4-dihydro-1H- isoquinolin-2-yl)butyl]benzamide 2 (RHM-1) represent leads for tumor diagnosis, given their high affinity at sigma2 receptors. With the purpose of obtaining good candidates for sigma2 PET tracers development, hybrid structures between 1 and 2 were designed. Excellent sigma1/ sigma2 selectivities were reached when 6,7- dimethoxytetrahydroisoquinoline was linked to an o-methoxy substituted arylamide (11a, 12a, 15a), and for these benzamides an intramolecular H-bond in the active conformation at the sigma sites, was hypothesized. However these excellent sigma2 ligands were accompanied by interaction with P-gp, which may limit their use as sigma2 receptor PET agents when tumors overexpress P-gp. Compound 15a whose P-gp interaction was just moderate represents an interesting tool for the development of sigma2 PET tracers useful in tumors overexpressing P-gp.

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

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1-magnesiotetrahydroisoquinolyloxazolines as chiral nucleophiles in stereoselective additions to aldehydes: Auxiliary optimization, asymmetric synthesis of (+)-corlumine, (+)-bicuculline, (+)-egenine, and (+)-corytensine, and preliminary 13C NMR studies of 1-lithio- and 1-magnesiotetrahydroisoquinolyloxazolines

Transmetalation of 1-lithiotetrahydroisoquinolyloxazolines with magnesium halides affords Grignard reagents that add to aldehydes with up to 80% selectivity for one of the four possible diastereomeric products. An oxazoline chiral auxiliary derived from camphor provides an optimal blend of diastereoselectivity and isomer separability. Synthetic applications of the optimal auxiliary, patterned after a literature approach in the racemic series, comprise an improved (formal) synthesis of bicuculline, egenine, and corytensine, as well as an efficient synthesis of corlumine. Preliminary NMR studies show that both 1-lithio- and 1-magnesiotetrahydroisoquinolyloxazolines are dynamic mixtures in THF solution at low temperatures. The barrier to pyramidal inversion of the secondary Grignard reagent is in the 9.8-10.1 kcal/mol range, while an upper limit of about 8.2 kcal/mol can be assigned to the barrier to the organolithium inversion.

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