Use of Tetraethyl Dimethylaminomethylenediphosphonate in the Synthesis of Benzothiophene-2-acetic Acid and Other Carboxylic Acids

Degenhardt, Charles R.

doi:10.1080/00397918208065945

Cited by 28 publications

(13 citation statements)

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“…was obtained from 2-(naph thalen-1-yl)acetic acid and N-(4-methoxybenzylidene)-3,4,5-trimethoxybenzenamine (8a) as a pale yellow crystalline powder 4.1.12. General method IV for preparation of b-lactams [28][29] To a solution of the appropriately protected phenol (10 mmol) in THF (50 mL) was added 1.5 equiv of 1 M tetrabutylammonium fluoride. The solution was stirred in an ice-bath for 15 min.…”

Section: General Methods II For B-lactam Preparationmentioning

confidence: 99%

“…28 It was previously reported that the most convenient and efficient method to produce this aminodiphosphonate reagent was the reaction of dimethylchloroformiminium chloride with 2.2 equivalents of triethyl phosphite. 29 The in situ generated iminium ion reacts with triethyl phosphite to generate 4 in high yields of up to 76% (Scheme 1). This reagent reacts with the aldehyde of interest to form an enamine phosphonate, which is hydrolysed with strong acid to produce the substituted acetic acids 5a and 5b (Scheme 1).…”

Section: Chemistrymentioning

confidence: 99%

“…This was obtained as a brown oil from [1-dimethylamino-2-(5-methylthiophen-2-yl)-vinyl]-phosphonic acid diethyl ester (1% yield) and was used immediately in the subsequent reaction without further purification;29 IR (KBr disk) m max : 1705.90 cm À1 (-C@O); 1 H NMR (400 MHz, CDCl 3 ) d 2.49 (s, 3H, CH 3 ), 3.83 (s, 2H, CH 2 ), 6.65 (d, 1H, J = 2.52, ArH), 6.77 (d, 1H, J = 2.52, ArH); 13 C NMR (100 MHz, CDCl 3 ) d 15.29 (CH 3 ), 35.25 (CH 2 ), 124.99, 127.19, 131.63, 139.95, 177.04 (C@O).…”

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confidence: 99%

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Synthesis, evaluation and structural studies of antiproliferative tubulin-targeting azetidin-2-ones

O’Boyle

Greene

Bergin

et al. 2011

Bioorganic & Medicinal Chemistry

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A series of azetidin-2-ones substituted at positions 1, 3 and 4 of the azetidinone ring scaffold were synthesised and evaluated for antiproliferative, cytotoxic and tubulin-binding activity. In these compounds, the cis double bond of the vascular targeting agent combretastatin A-4 is replaced with the azetidinone ring in order to enhance the antiproliferative effects displayed by combretastatin A-4 and prevent the cis/trans isomerisation that is associated with inactivation of combretastatin A-4. The series of azetidinones was synthetically accessible via the Staudinger and Reformatsky reactions. Of a diverse range of heterocyclic derivatives, 3-(2-thienyl) analogue 28 and 3-(3-thienyl) analogue 29 displayed the highest potency in human MCF-7 breast cancer cells with IC(50) values of 7 nM and 10nM, respectively, comparable to combretastatin A-4. Compounds from this series also exhibited potent activity in MDA-MB-231 breast cancer cells and in the NCI60 cell line panel. No significant toxicity was observed in normal murine breast epithelial cells. The presence of larger, bulkier groups at the 3-position, for example, 3-naphthyl derivative 21 and 3-benzothienyl derivative 26, resulted in relatively lower antiproliferative activity in the micromolar range. Tubulin-binding studies of 28 (IC(50)=1.37 μM) confirmed that the molecular target of this series of compounds is tubulin. These novel 3-(thienyl) β-lactam antiproliferative agents are useful scaffolds for the development of tubulin-targeting drugs.

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Section: General Methods II For B-lactam Preparationmentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

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confidence: 99%

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Synthesis, evaluation and structural studies of antiproliferative tubulin-targeting azetidin-2-ones

O’Boyle

Greene

Bergin

et al. 2011

Bioorganic & Medicinal Chemistry

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“…Likewise, substituted aminomethylene biphosphonates are also an important class of biologically active compounds, and much work has been reported in the recent literature on the synthesis and reactivity of such compounds [2][3][4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

The reaction of PhCH2C(O)NR2/P(O)Cl3 with phosphites and hydridophosphorane

Wang

Cao

et al. 2000

Heteroatom Chem.

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“…Much work has been reported in recent literature on the synthesis, reactivity, and bioactivity of alkylaminomethylenediphosphonates [1][2][3][4][5][6][7]. Among numerous synthetic methods, two reports have detailed the reaction of dimethylchloroformiminium chloride with triethyl phosphite to give tetraethyl dimethylaminomethylenediphosphonate 1 (Scheme 1) [3,8].…”

Section: Introductionmentioning

confidence: 99%