15547-66-7

Upstream product

• 100-07-2 4-methoxy-benzoyl chloride 
• 120-20-7 2-(3,4-dimethoxyphenyl)-ethylamine 
• 3424-93-9 4-methoxyphenylacetamide 
• 696-63-9 4-Methoxybenzenethiol 
• 201230-82-2 carbon monoxide 
• 1541168-57-3 N-[2-(3,4-dihydroxyphenyl)ethyl]-4-methoxybenzamide 
• 74-88-4 methyl iodide 
• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 4230-93-7 3,4-dimethoxynitrostyrene 

Downstream Products

• 15462-83-6 6,7-dimethoxy-1-<(para-methoxy)phenyl>-3,4-dihydroisoquinoline 
• 15547-67-8 6,7-dimethoxy-1-(4-methoxy-phenyl)-isoquinoline 
• 70319-15-2 (±)-6,7-dimethoxy-1-(4-methoxyphenyl)-N-methyl-1,2,3,4-tetrahydroisoquinoline 
• 1448701-61-8 (+)-6,7-dimethoxy-1-(4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline 

Relevant academic research and scientific papers

Cobalt catalysed aminocarbonylation of thiols in batch and flow for the preparation of amides

The synthesis of amides from thiols through a cobalt-catalyzed aminocarbonylation is shown. After optimizing all the reaction parameters, the methodology makes possible the obtention of amides with variable yields, while competing reactions such as the formation of disulfides and ureas can be limited. The process works well with aromatic thiols with electron donating groups (EDG) whereas other thiols give reaction with lower yields. The previous process has been transferred and optimized into flow equipment, thus allowing using less CO in a safer way, and permitting the scaling up of the synthesis. Two drugs, moclobemide and itopride were prepared with this methodology, albeit only in the second case with good results. A mechanistic pathway is proposed.

Asymmetric Transfer Hydrogenation of Unhindered and Non-Electron-Rich 1-Aryl Dihydroisoquinolines with High Enantioselectivity

The use of arene/Ru/TsDPEN catalysts bearing a heterocyclic group on the TsDPEN in the asymmetric transfer hydrogenation (ATH) of dihydroisoquinolines (DHIQs) containing meta- or para-substituted aromatic groups at the 1-position results in the formation of products of high enantiomeric excess. Previously, only 1-(ortho-substituted)aryl DHIQs, or with an electron-rich fused ring gave products with high enantioselectivity; therefore, this approach solves a long-standing challenge for imine ATH.

Josiphos-Type Binaphane Ligands for Iridium-Catalyzed Enantioselective Hydrogenation of 1-Aryl-Substituted Dihydroisoquinolines

Convenient synthesis and useful application of a series of Josiphos-type binaphane ligands were described. The iridium complexes of these chiral diphosphines displayed excellent enantioselectivity and good reactivity in the asymmetric hydrogenation of challenging 1-aryl-substituted dihydroisoquinoline substrates (full conversions, up to >99% ee, 4000 TON). The use of 40% HBr (aqueous solution) as an additive dramatically improved the asymmetric induction of these catalysts. This transformation provided a highly efficient and enantioselective access to chiral 1-aryl-substituted tetrahydroisoquinolines, which were of great importance and common in natural products and biologically active molecules.

Enantioselective Synthesis of 1-Aryl-Substituted Tetrahydroisoquinolines Through Ru-Catalyzed Asymmetric Transfer Hydrogenation

A convenient and general asymmetric transfer hydrogenation of a wide array of 1-aryl-3,4-dihydroisoquinoline derivatives using a [RuIICl(η6-benzene)TsDPEN] complex in combination with a 5:2 HCOOH-Et3N azeotropic mixture as a hydrogen source was developed. Under mild reaction conditions, the described catalytic transformation secured a practical synthetic access to the corresponding valuable chiral 1-aryltetrahydroisoquinoline units with high atom economy, a broad substrate scope, high isolated yields (up to 97%) and good to excellent enantioselectivities (up to 99% ee). It was found that the stereochemical outcome of the reaction was strongly influenced by both the structure of the catalyst and the substituents present on the substrate. The synthetic utility of the present protocol has been demonstrated through the asymmetric synthesis of several biologically important alkaloids including the antiepileptic drug agent 1c, as well as (-)-nor-cryptostyline alkaloids I and II.

Rhodium catalyzed cyanation of chelation assisted C-H bonds

A rhodium-catalyzed cyanation of chelation assisted C-H bonds is described employing N-cyano-N-phenyl-p-methylbenzenesulfonamide as an efficient cyanating reagent. The present method allowed the synthesis of various benzonitirle derivatives in good to excellent yield. A number of chelating groups are also effective in the present cyanation of C-H bonds. In addition, the developed methodology was applied in the formal synthesis of the isoquinoline alkaloid, menisporphine.

Chelation-assisted palladium-catalyzed direct cyanation of 2-arylpyridine C-H bonds

A chelation-assisted palladium-catalyzed ortho-cyanation of the sp 2 C-H bond by CuCN provided aromatic nitriles In moderate to good yields. Notably, the reaction could be conducted on a 10 mmol scale. The key Intermediate of the natural produc

Structure-based approach to falcipain-2 inhibitors: Synthesis and biological evaluation of 1,6,7-Trisubstituted dihydroisoquinolines and isoquinolines

1,4,7-Trisubstituted isoquinolines were designed, synthesized and evaluated for their inhibition against Plasmodium falciparum cysteine protease falcipain-2. The 1-benzyloxyphenyl-dihydroisoquinoline and -isoquinoline derivatives were found to exhibit better activity against falcipain-2 than their corresponding 1-hydroxyphenyl or 1-methoxyphenyl analogues. The docking scores correlate with the IC50 values of compounds and give a high coefficient correlation of 0.94.

Synthesis and spectral properties of 6,7-dimethoxy-1-[(ortho; and para-R)-phenyl]-3,4-dihydroisoquinoline

The preparation of eleven novel 6,7-dimethoxy-1-[(ortho, and para-R)-phenyl]-3,4-dihydroisoquinolines with possible pharmacological activity is described. The structure of all products was corroborated by ir, 1H nmr, 13C-nmr, and ms.

The mechanism of the Bischler-Napieralski Reaction

The Bischler-Napieralski dihydroisoquinoline synthesis was proven to occur via imidoyl chlorides and the corresponding nitrilium salt.Two-step process required much milder conditions (20 degC - 50 degC) compared to drastic classical conditions of refluxing at 100 degC - 200 degC.The Bischler-Napieralski reaction is shown to share a common intermediate with two other well-known reactions: the von Braun and the Ritter reactions