40523-36-2

Upstream product

• 40523-32-8 3-(phenylmethylene)isoindol-1-one 
• 74-88-4 methyl iodide 
• 40523-35-1 (3E)-3-benzylidene-2-methylisoindolin-1-one 
• 110166-72-8 2-(2'-phenylethynyl)-N-methyl benzamide 
• 4770-23-4 3-benzyl-3-hydroxy-2-methyl-1,3-dihydroisoindol-1(3H)-one 
• 206365-69-7 3-(hydroxy(phenyl)methyl)-2-methylisoindolin-1-one 
• 58084-22-3 2-iodo-N-methyl-benzamide 
• 637-44-5 phenylpropyolic acid 
• 88-67-5 2-Iodobenzoic acid 
• 536-74-3 phenylacetylene 
• 3930-83-4 o-iodobenzamide 
• 550-44-7 N-methylphthalimide 
• 100-52-7 benzaldehyde 
• 4702-13-0 N-phthaloylglycine 

Relevant academic research and scientific papers

Ultrasound assisted Cu-catalyzed decarbonylative Sonogashira coupling-cyclization strategy: Synthesis and evaluation of 3-heteroarylmethylene isoindolin-1-ones against SIRT1

Prompted by the reported HDAC1 inhibition / anticancer properties of 3-methyleneisoindolin-1-one derivatives a series of 3-heteroarylmethylene substituted isoindolin-1-ones were explored as potential inhibitors of SIRT1. A sonochemical approach based on the Cu(I)-catalyzed decarbonylative Sonogashira coupling-cyclization strategy was developed for accessing this class of compounds. The approach involved a faster and milder synthesis of 3-heteroarylmethylene isoindolin-1-ones with high regioselectivity via cross-coupling of 2-iodobenzamides with heteroaryl alkynyl acids followed by 5-exo-dig heteroannulation in the same pot. The methodology was latter extended to the synthesis of 3-arylmethylene isoindolin-1-ones when the desired products were obtained in acceptable yield. When tested for the SIRT1 inhibitory potential in vitro some of the 3-heteroarylmethylene isoindolin-1-ones showed good activities with the compound 3e appeared as best among them whereas 3-aryl analogues were found to be less active. According to the SAR analysis the order of effectiveness of heteroaryl moieties appeared as imidazol-5-yl > pyridin-2-yl > indol-5-yl > thiophen-2-yl > pyridin-3-yl > furan-3-yl. The in silico docking studies not only highlighted the key role of the carbonyl oxygen of isoindolin-1-one ring in interacting with SIRT1 via H-bond formation but also indicated important involvements of other hydrophobic interactions. Based on the in vitro and in silico studies the compound 3e emerged as an initial hit for further pharmacological evaluation.

Phosphazene Superbase-Mediated Regio- and Stereoselective Iodoaminocyclization of 2-(1-Alkynyl)benzamides for the Synthesis of Isoindolin-1-ones

Phosphazene superbase P4-t-Bu mediated iodoaminocyclization of 2-(1-alkynyl)benzamides is reported. The reaction works under ambient conditions and instantaneously results in the synthesis of isoindolin-1-ones in 65-97% yields, in a regio- and stereoselective manner. The exclusive formation of products with Z-geometry (across the exo C?C bond) has been confirmed through X-ray crystallography. The methodology also provides an easy access to aristolactams, an important class of natural products. This has been successfully demonstrated by synthesizing two aristolactam derivatives (including Cepharanone B).

Direct Difluorination-Hydroxylation, Trifluorination, and C(sp2)-H Fluorination of Enamides

A direct double functionalization involving both difluorination and hydroxylation of enamides is reported. With the appropriate combination of an electrophilic fluorinating reagent and H2O, the most convenient and ecofriendly hydroxylating agent, the preparation of 3-(difluoroalkyl)-3-hydroxyisoindolin-1-ones was achieved under basic or Br?nsted acidic conditions. Suitable conditions for trifluorination as well as C(sp2)-H fluorination were also identified. Subsequent asymmetric functionalization of the obtained gem-difluorinated products has also been demonstrated.

C(sp2)-H Trifluoromethylation of enamides using TMSCF3: Access to trifluoromethylated isoindolinones, isoquinolinones, 2-pyridinones and other heterocycles

A method for the direct C(sp2)-H trifluoromethylation of enamides, including biologically relevant isoindolinones, isoquinolinones and 2-pyridinones using TMSCF3 under oxidative conditions is presented. The protocol is convenient, operationally simple and exhibits high tolerance across a multitude of relevant handles and functional groups.

Synthesis of 3-substituted isoindolin-1-ones via a tandem desilylation, cross-coupling, hydroamidation sequence under aqueous phase-transfer conditions

A simple and expedient method for the synthesis of 3-methylene-isoindolin-1-ones 4 under aqueous phase-transfer conditions has been developed. Starting from 2-iodobenzamides 1 and (silyl)alkynes, the products are obtained in high yields and short reaction times (30 min) with the use of inexpensive CuCl/PPh3 catalyst system in the presence of n-Bu4NBr (TBAB) as a phase-transfer agent. Terminal alkynes are conveniently "unmasked" upon in situ desilylation under the reaction conditions. Alkynes possessing heterocyclic moieties were also found as amenable substrates. Furthermore, a one-pot process starting from 2-iodobenzamides 1, aryl halides (bromides or iodides) and trimethylsilylacetylene (TMSA) as a convenient acetylene surrogate was also shown to be feasible under Pd/Cu catalysis.

Reductive coupling of phthalimides with ketones and aldehydes by low-valent titanium: One-pot synthesis of alkylideneisoindolin-1-ones

The reductive coupling of phthalimides with ketones and aldehydes by Zn-TiCl4 in THF gave two- and four-electron reduced products, 3-hydroxy-3-(1-hydroxyalkyl)isoindolin-1-ones and alkylideneisoindolin-1-ones, selectively by controlling the rea

Electroreductive intermolecular coupling of phthalimides with aldehydes: Application to the synthesis of alkylideneisoindolin-1-ones

The electroreduction of N-methyl, N-p-anisyl, and N-unsubstituted phthalimides with aldehydes in the presence of chlorotrimethylsilane and triethylamine gave intermolecularly coupled products, 3-hydroxy-3-(1- hydroxyalkyl)isoindolin-1-ones. The coupling p

Microphotochemistry: 4,4′-dimethoxybenzophenone mediated photodecarboxylation reactions involving phthalimides

A series of 4,4'-dimethoxybenzophenone mediated intra- and intermolecular photodecarboxylation reactions involving phthalimides have been examined under microflow conditions. Conversion rates, isolated yields and chemoselectivities were compared to analogous reactions in a batch photoreactor. In all cases investigated, the microreactions gave superior results thus proving the superiority of microphotochemistry over conventional technologies.

A tandem elimination-cyclization-suzuki approach: Efficient one-pot synthesis of functionalized (Z)-3-(arylmethylene)isoindolin-1-ones

(Chemical Equation Presented) A novel and efficient one-pot regioselective elimination-cyclization-Suzuki approach was developed to afford (Z)-3-arylmethyleneisoindolin-1-ones in good to excellent yields from easily accessible o-gem-dihalovinylbenzamides and organoboron reagents.

Palladium-catalysed heteroannulation with terminal alkynes: A highly regio- and stereoselective synthesis of (Z)-3-aryl(alkyl)idene isoindolin-1- ones

A highly regio- and stereoselective method for the synthesis of (Z)-3- aryl(alkyl)idene isoindolin-1-ones through palladium-copper catalysis is described. 2-Iodobenzamide 1 and its substituted derivatives 2-10 were reacted with terminal alkynes 11-19 in the presence of (PPh3)2PdCl2, CuI, and Et3N in DMF mostly at 80°C for 16 h to yield the 2-alkynyl substituted benzamides 20-38, 40-45, 77 which could then be cyclised with NaOEt in EtOH to the 3-aryl(alkyl)idene isoindolin-1-ones 46-49, 51, 53-55, 57, 59-71, 73 and 75. In certain cases, the isoindolin-1-ones 50, 52, 56 and 58 could be directly obtained by the palladium-catalysed reactions. (C) 2000 Elsevier Science Ltd.