19013-07-1

Basic information

• Product Name: 2,2-Dimethyl-6-acetyl-2H-1-benzopyran
• Synonyms: 2,2-Dimethyl-6-acetyl-2H-1-benzopyran;6-Acetyl-2,2-dimethyl-2H-1-benzopyran;6-Acetyl-2,2-dimethyl-3-chromene;Demethoxyencecalin;Desmethoxyencecalin;Methyl(2,2-dimethyl-2H-1-benzopyran-6-yl) ketone;1-(2,2-Dimethyl-2H-chromen-6-yl)-ethanone;2,2-diMethyl-2H-chroMene
• CAS NO: 19013-07-1
• Molecular Formula: C₁₃H₁₄O₂
• Molecular Weight: 202.2491
• Mol File: 19013-07-1.mol
• Article Data: 19

Chemical Properties

• Boiling Point: 329.775 °C at 760 mmHg
• Flash Point: 147.718 °C
• Appearance: colorless transparent liquid or white solid
• Density: 1.061 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.531
• CAS DataBase Reference: 2,2-Dimethyl-6-acetyl-2H-1-benzopyran(CAS DataBase Reference)
• NIST Chemistry Reference: 2,2-Dimethyl-6-acetyl-2H-1-benzopyran(19013-07-1)
• EPA Substance Registry System: 2,2-Dimethyl-6-acetyl-2H-1-benzopyran(19013-07-1)

Safety Data

• Hazardous Substances Data: 19013-07-1(Hazardous Substances Data)

Usage

Synthesis Reference(s)

Journal of Heterocyclic Chemistry, 32, p. 219, 1995 DOI: 10.1002/jhet.5570320136Synthesis, p. 144, 1979 DOI: 10.1055/s-1979-28595

InChI:InChI=1/C13H14O2/c1-9(14)10-4-5-12-11(8-10)6-7-13(2,3)15-12/h4-8H,1-3H3

Upstream product

• 33143-29-2 6-cyano-2,2-dimethylchromene 
• 107-86-8 3,3-dimethyl acrylaldehyde 
• 122-51-0 orthoformic acid triethyl ester 
• 99-93-4 4-Hydroxyacetophenone 
• 78-79-5 isoprene 
• 155853-32-0 3-methyl-1-<2(tetrahydropyran-4-yloxy)-5-(2-methyl-(1,3)-dithian-2-yl)phenyl>-2-butenol 
• 155853-31-9 2-methyl-2-(4-tetrahydropyran-4-yloxy)-(1,3)-dithiane 
• 155853-29-5 2-methyl-2-(4-methoxymethylenoxyphenyl)-(1,3)dioxolane 
• 155853-28-4 2-methyl-2-(4-hydroxyphenyl)-1,3-dithiane 
• 36881-01-3 2-(4-hydroxyphenyl)-2-methyl-1,3-dioxolane 
• 157953-26-9 Benzoic acid 4-acetyl-2-(3-methyl-but-2-enyl)-phenyl ester 
• 157953-15-6 1-(4-benzyloxy-3-iodophenyl)ethanone 
• 81944-40-3 4-hydroxy-3-(3'-hydroxyisopentyl)acetophenone 
• 54696-05-8 4'-benzyloxy-acetophenone 

Downstream Products

• 32333-31-6 2,2-dimethyl-6-acetylchroman 
• 77346-67-9 4-hydroxy-2,2-dimethyl-6-acetylchromane 
• 71822-00-9 <1-hydroxyethyl>-2,2-dimethylchromene 
• 171596-62-6 (3R,4R)-6-acetyl-2,2-dimethyl-3,4-epoxy-2H-1-benzopyran 
• 178458-56-5 (3S,4S)-6-acetyl-2,2-dimethyl-3,4-epoxy-2H-1-benzopyran 

Relevant articles and documents

A New Electrosynthesis of 2,2-Dimethylchromenes from 2-(1-Bromo-1-methylethyl)benzofurans

Electrolytic reduction of 2-(1-bromo-1-methylethyl)benzofurans in acetonitrile affords the corresponding 2,2-dimethylchromenes in good yields even in the absence of a proton donor and comprises the cleavage of a carbon-bromine bond followed by ring expansion.

Continuous processing to control a potentially hazardous process: Conversion of aryl 1,1-dimethylpropargyl ethers to 2,2-dimethylchromenes (2,2-dimethyl-2H-1-benzopyrans)

The thermal Claisen rearrangement of 4-cyanophenyl 1,1-dimethylpropargyl ether (4) to 6-cyano-2,2-dimethylchromene (5), (6-cyano-2,2-dimethyl-2H-1-benzopyran), which is used in the synthesis of a potassium channel activator drug candidate, BMS-180448, created a significant process development issue. The resulting large heat release in this conversion posed not only a safety risk but could also cause product degradation if done in a batch-wise manner. The solution was to exploit the high surface-to-volume ratio of a plug-flow reactor that would maximize the heat transfer, thereby permitting tight and responsive temperature with better reaction control. In the course of successfully testing the plug-flow concept on "micro"-flow scale (gram quantity) and "kilo"-flow scale (～10 kg), a generalized mathematical model capable of predicting the reaction performance based on the physical properties of any given plug-flow reactor was generated. The model provides requisite information to design and operate a plug-flow reactor of any size for this reaction. This model would optimize reaction conditions for an acquired reactor system capable of producing ～7 kg/h of the dimethylchromene. Application of plug-flow reactor technology enabled production of high quality 2,2-dimethylchromenes in good yield (>98 mol %) without the use of solvents and with virtually no waste streams.

Identification of anticancer agents based on the thieno[2,3-b]pyridine and 1H-pyrazole molecular scaffolds

Structural similarity search of commercially available analogues of thieno[2,3-b]pyridine and 1H-pyrazole derivatives, known anticancer agents, resulted in 717 hits. These were docked into the phosphoinositide specific-phospholipase C (PLC) binding pocket, the putative target of the compounds, to further focus the selection. Thirteen derivatives of the thieno[2,3-b]pyridines were identified and tested against the NCI60 panel of human tumour cell lines. The most active derivative 1 was most potent against the MDA-MB-435 melanoma cell line with GI50at 30?nM. Also, it was found that a piperidine moiety is tolerated on the thieno[2,3-b]pyridine scaffold with GI50?=?296?nM (MDA-MB-435) for derivative 10 considerably expanding the structure activity relationship for the series. For the 1H-pyrazoles four derivatives were identified using the in silico approach and additionally ten were synthesised with various substituents on the phenyl moiety to extend the structural activity relationship but only modest anticancer activity was found.

NOVEL COMPOUND OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT

The present invention relates to a novel compound inhibiting Hsp 90 and to a pharmaceutical composition including same as an active ingredient. Compounds of formula 1 and formula 2 according to the present invention inhibit the accumulation of HIF-1α protein, which is an Hsp90 client protein, by suppressing Hsp90 expression, and effectively inhibit the activity of vascular endothelial growth factor (VEGF). Furthermore, said compounds have low cytotoxicity and can thus be used as an active ingredient for the treatment of diabetic retinopathy and arthritis.

NOVEL COMPOUND OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT

The present invention relates to a compound inhibiting Hsp90 and a pharmaceutical composition comprising the same as an active ingredient. The compounds represented by formula 1 and formula 2 of the present invention suppress the expression of Hsp90 so that they can inhibit the accumulation of HIF-1α, the Hsp90 client protein, and also efficiently inhibit the activation of VEGF. In addition, these compounds display low cytotoxicity, so that they can be effectively used as an active ingredient of an anti-cancer agent, a diabetic retinopathy treating agent, and an anti-arthritic agent.

Identification of small molecule inhibitors of the STAT3 signaling pathway: Insights into their structural features and mode of action

A series of novel STAT3 inhibitors consisting of Michael acceptor has been identified through assays of the focused in-house library. In addition, their mode of action and structural feature responsible for the STAT3 inhibition were investigated. In parti

Natural product-like combinatorial libraries based on privileged structures. 1. General principles and solid-phase synthesis of benzopyrans

Herein we report a novel strategy for the design and construction of natural and natural product-like libraries based on the principle of privileged structures, a term originally introduced to describe structural motifs capable of interacting with a variety of unrelated molecular targets. The identification of such privileged structures in natural products is discussed, and subsequently the 2,2-dimethylbenzopyran moiety is selected as an inaugural template for the construction of natural product-like libraries via this strategy. Initially, a novel solid-phase synthesis of the benzopyran motif is developed employing a unique cycloloading strategy that relies on the use of a new, polystyrene-based selenenyl bromide resin. Once the loading, elaboration, and cleavage of these benzopyrans was established, this new solid-phase method was then thoroughly validated through the construction of six focused combinatorial libraries designed around natural and designed molecules of recent biological interest.

Process for the production of 2H-1-benzopyrans

There is provided a 2-stage process for making 2H-1-benzopyrans wherein an alpha,beta-unsaturated aldehyde is reacted with an alkanol or an alkane-diol in the presence of a dehydrating compound which is an orthoformate and an aluminum oxide/silicon oxide catalyst to form an aliphatic acetal, which is then condensed in a second stage with a phenol in the presence of base in an organic solvent.

Cyclization of o-(3-hydroxy-3-methylbutynyl)-phenols with boron tribromide to 4-bromo-2,2-dimethylchromenes and their electroreduction to 2,2-dimethylchromenes

Cyclization of o-(3-hydroxy-3-methylbutynyl)phenols (2) with boron tribromide gave easily 4-bromo-2,2-dimethylchromenes (3). Electrolytic reduction of 3 at a Hg-pool electrode afforded the corresponding 2,2-dimethylchromenes (6) in high yields.

Synthesis of 6-Cyano-2,2-dimethyl-2H-1-benzopyran and Other Substituted 2,2-dimethyl-2H-1-benzopyrans

A practical synthesis of 6-cyano-2,2-dimethyl-2H-1-benzopyran (1) has been developed.This process involves the pyridine-catalyzed condensation of 1,1-diethoxy-3-methyl-2-butene (6) with 4-cyanophenol (3) in toluene or xylene at elevated temperatures.The development of this process, including an evaluation of solvents, bases, acid catalysts, and alterantive acetals, along with an improved synthesis of 1,1-diethoxy-3-methyl-2-butene, is discussed.Using this method, a variety of other substituted 2,2-dimethyl-2H-1-benzopyrans were synthesized.