53666-76-5

Usage

Synthesis

4-Hydroxy-5-methoxy-2H-1-benzopyran-2-one is obtaned by 2-Hydroxy-5-methoxy-acetophenone with sodium hydride in diethyl carbonate.2-Hydroxy-5-methoxy-acetophenone (1.50 g, 9.03 mmol) in diethyl carbonate (8.3 ml) was added dropwise into a suspension of sodium hydride (60% dispersion in mineral oil, 1.81 g, 45.2 mmol) in diethyl carbonate (8.3 ml) and heated under reflux at 100 ?C for 3 hours. The resultant mixture was left to cool to 0 ?C in an ice bath and quenched by dropwise addition of water until effervescence ceased. The aqueous layer was washed with diethyl ether (3 × 16 ml) then acidified using concentrated hydrochloric acid to pH 1. The precipitate was filtered and washed with water, followed by petroleum ether and left to dry overnight at 90 ?C to give the title compound as a colourless solid (902 mg, 52%): mp: 150 – 153 ?C (Lit.: 155 ?C); vmax/cm-1 3207bw (O-H), 1727s (C=O), 1655m (C=C), 1606s (aro. ring C=C); δH (300 MHz; DMSO-d6) 11.34 (1H, br. s., OH), 7.57 (1H, t, J 8.4, C(7)H), 6.95 (2H, d, J 8.4, C(6)H and C(8)H), 5.51 (1H, s, C(3)H), 3.90 (1H, s, OCH3); δC (75 MHz; DMSO-d6) 167.2 (Ar-C), 161.4 (Ar-C), 157.3 (Ar-C), 155.2 (Ar-C), 133.0 (Ar-CH), 109.2 (Ar-CH), 106.8 (Ar-CH), 105.0 (Ar-C), 90.8 (C(3)H), 56.5 (OCH3); m/z (-ES) 191 (100%, [M-H]-).

Upstream product

• 703-23-1 2'-hydroxy-6'-methoxyacetophenone 
• 105-58-8 Diethyl carbonate 
• 211449-28-4 Diethyl-carbamic acid 2-acetyl-3-methoxy-phenyl ester 
• 85630-17-7 3-methoxyphenyl N,N-diethylcarbamate 

Downstream Products

• 53666-77-6 4,5-dimethoxy-coumarin 
• 30992-74-6 4,5-dihydroxy-2H-benzopyran-2-one 
• 1609132-85-5 C₃₈H₂₆O₄ 
• 1560773-72-9 (S)-4-[3-(2-amino-3-hydroxypropanoylamino)-4-methoxyphenyl]-5-methoxycoumarin hydrochloride 
• 1560773-61-6 (S)-4-{3-[3-benzyloxy-2-(tert-butoxycarbonylamino)propanoylamino]-4-methoxyphenyl}-5-methoxycoumarin 
• 1560773-49-0 4-(3-amino-4-methoxyphenyl)-5-methoxycoumarin 
• 1560773-38-7 4-(3-amino-4-methoxyphenyl)-5-methoxycoumarin hydrochloride 
• 1560773-27-4 4-(3-tert-butoxycarbonylamino-4-methoxyphenyl)-5-methoxycoumarin 
• 36914-76-8 5-Methoxy-4-phenyl-2H-1-benzopyran-2-one 
• 142732-56-7 4-hydroxy-5-methoxy-3-(3-methoxyphenyl)-1-benzopyran-2-one 
• 124010-44-2 4-hydroxy-5-methoxy-3-(2,4,6-trimethoxyphenyl)-1-benzopyran-2-one 
• 124010-48-6 3-(2,4-dimethoxyphenyl)-4-hydroxy-5-methoxy-1-benzopyran-2-one 
• 124010-45-3 3-(3,4-dimethoxyphenyl)-4-hydroxy-5-methoxy-1-benzopyran-2-one 
• 142732-55-6 4-hydroxy-5-methoxy-3-(2-methoxyphenyl)-1-benzopyran-2-one 

Relevant academic research and scientific papers

TRICYCLIC COMPOUNDS ACTING ON CRBN PROTEINS

The present invention discloses a series of tricyclic compounds and use thereof in preparing a medicament for treating a disease related to CRBN protein. Specifically, the present invention discloses a derivative compound of formula (1) or a pharmaceutically acceptable salt thereof.

Copper(II)-Catalyzed Tandem Reaction: Synthesis of Furo[3,2- c]coumarin Derivatives and Evaluation for Photophysical Properties

An efficient protocol for synthesizing furo[3,2-c]coumarin derivatives is described. The novel reaction could afford the desired furocoumarins with good to excellent yields in a mild and rapid manner. Large substrate scope screening and scale-up preparation have also been accomplished, and selected compounds were evaluated for their photophysical properties.

Mechanistic studies on the palladium-catalyzed cross-dehydrogenative coupling of 4-phenoxy-2-coumarins: Experimental and computational insights

Delineating the mechanistic features of C-H activation in aryl-heteroaryl coupling is an important step in the design of selective, catalytic processes. Herein we use the intramolecular dehydrogenative coupling of 4-phenoxy-2-coumarins as a model study. Computational results and experimental studies suggest that CMD is operative in the cleavage of both C-H bonds, and that the heteroaryl C-H is cleaved initially.

Palladium-catalyzed [2+2+1] oxidative annulation of 4-hydroxycoumarins with unactivated internal alkynes: Access to spiro cyclopentadiene-chroman-2,4-dione complexes

Herein, we report our new results regarding a palladium-catalyzed [2+2+1] oxidative annulation of 4-hydroxycoumarins with unactivated internal alkynes, which affords a new class of compounds: the spiro cyclopentadiene-chroman-2,4- diones.

Synthesis and biological evaluation of coumarin-based inhibitors of NAD(P)H: Quinone oxidoreductase-1 (NQO1)

The synthesis is reported here of two novel series of inhibitors of human NAD(P)H quinone oxidoreductase-1 (NQO1), an enzyme overexpressed in several types of tumor cell. The first series comprises substituted symmetric dicoumarol analogues; the second series contains hybrid compounds where one 4-hydroxycoumarin systemis replaced by a different aromatic moiety. Several compounds show equivalent or improved NQO1 inhibition over dicoumarol, both in the presence and in the absence of added protein. Further, correlation is demonstrated between the ability of these agents to inhibit NQO1 and computed binding affinity. We have solved the crystal structure of NQO1 complexed to a hybrid compound and find good agreement with the in silico model. For both MIA PaCa-2 pancreatic tumor cells and HCT116 colon cancer cells, dicoumarol shows the greatest toxicity of all compounds. Thus, we provide a computational, synthetic, and biological platform to generate competitive NQO1 inhibitors with superior pharmacological properties to dicoumarol. This will allow a more definitive study of NQO1 activity in cells, in particular, its drug activating/detoxifying properties and ability to modulate oncoprotein stability. 2009 American Chemical Society.

Selective benzopyranone and pyrimido[2,1-α]isoquinolin-4-one inhibitors of DNA-dependent protein kinase: Synthesis, structure-activity studies, and radiosensitization of a human tumor cell line in vitro

A diverse range of chromen-2-one, chromen-4-one and pyrimidoisoquinolin-4- one derivatives was synthesized and evaluated for inhibitory activity against the DNA repair enzyme DNA-dependent protein kinase (DNA-PK), with a view to elucidating structure-activity relationships for potency and kinase selectivity. DNA-PK inhibitory activity varied widely over the series of compounds evaluated (IC50 values ranged from 0.19 to >10 μM), with excellent activity being observed for the 7,8-benzochromen-4-one and pyrimido[2,1-a] isoquinolin-4-one templates. By contrast, inhibitors based on the benzochromen-2-one (coumarin) or 2-aryl-7,8-benzochromen-4-one (flavone) scaffolds were less potent. Crucially, these studies revealed a very constrained structure-activity relationship at the 2-position of the benzopyranone and pyrimido[2,1-a]-isoquinolin-4-one pharmacophore, with only a 2-morpholino or 2-(2′-methylmorpholino) group being tolerated at this position. More detailed biological studies conducted with the most potent inhibitor NU7163 (48; IC50 = 0.19 μM) demonstrated ATP-competitive DNA-PK inhibition, with a Ki value of 24 nM, and 48 exhibited selectivity for DNA-PK compared with the related enzymes ATM, ATR, mTOR, and PI 3-K (p110alpha). Compound 48 sensitized the HeLa human tumor cell line to the cytotoxic effects of ionizing radiation in vitro, a dose modification factor of 2.3 at 10% survival being observed with an inhibitor concentration of 5 μM. This study identified these structural classes as novel DNA-PK inhibitors and delineated initial structure-activity relationships against DNA-PK.

Directed ortho metalation-cross coupling links. Carbamoyl rendition of the Baker-Venkataraman rearrangement. Regiospecific route to substituted 4- hydroxycoumarins

A new carbamoyl Baker-Venkataraman rearrangement (4) which allows a general synthesis of substituted 4-hydroxycoumarins 8 in 43-82% overall yields is described; the intermediate arylketones 6 are efficiently prepared (59-91% yields) via a Directed ortho Metalation - Negishi cross coupling protocol from arylcarbamates 5 and the overall sequence provides a regiospecific anionic Friedel-Crafts complement for the construction of ortho-acyl phenols and coumarins.