Reagents, prototypes

The H + NO2 OH + NO reaetion provides an exeellent example of the use of laser fluoreseenee deteetion for the elueidation of the dynamies of a ehemieal reaetion. This reaetion is a prototype example of a radieal-radieal reaetion in that the reagents and produets are all open-shell free radieal speeies. Both the hydroxyl and nitrie oxide produets ean be eonveniently deteeted by eleetronie exeitation in the UV at wavelengths near 226 and 308 mn, respeetively. Atlases of rotational line positions for the lowest eleetronie band systems of these... 

H (high) indicates that under the conditions of the prototype reagent the protective group is readily removed to regenerate the original functional group. 

Reaction of estrone methyl ether with methyl Grignard reagent followed by Birch reduction and hydrolysis of the intermediate enol ether affords the prototype orally active androgen in the 19-nor series, normethandrolone (69). ° (Note that here again the addition of the methyl group proceeded stereoselectively by approach from the least hindered side.) The preparation of the ethyl homolog starts by catalytic reduction of mestranol treatment of the intermediate, 70, under the conditions of the Birch reduction and subsequent hydrolysis of the intermediate enol ether yields norethandrolone (71). ... 

The prototype of this series is synthesized by first reacting morphine with cyanogen bromide. This reagent in effect serves to replace the methyl group by cyano. Hydrolysis of the intermediate (11) affords desmethylmorphine (12). Alkylation of the last with allyl bromide affords nalorphine (13). ... 

In most cases, in consultation with the HTS group, the research area laboratory will develop a benchtop assay that is at least compatible with the HTS format of choice for their target. This tends to facilitate project transitions and provides a tool that the research area laboratory will use later to follow up hits and develop SAR. In other cases, the HTS assay development group will assume all responsibility for assay development. The formality of the transfer of the project from the research area to the HTS group varies between organizations, but the outcomes are quite similar. All of the details of the prototype assay are reviewed by both teams, and, where applicable, reagents, protocols, and even plates or pipette tips are exchanged. 

The reactions were carried out in sealed Pyrex tubes employing a prototype single-mode microwave cavity. The reagents were added to the resin-bound aryl halide under a nitrogen atmosphere and irradiated for the time periods indicated (Scheme 7.14). Rather short reaction times provided almost quantitative conversions, with minimal degradation of the solid support. 

Also termed ethyl acetoacetate, or CH3COCH2COOC2-H5. As an ester, it can be hydrolyzed under certain conditions to acetoacetic acid (CH3COCH2COOH) as a ketone, it reacts with reagents for the carbonyl (C = O) group. Peculiarly, it also behaves like a hydroxyl (OH-) compound. It is the prototype of the phenomenon of tautomerism, and its isomeric forms are termed the keto and the enol forms. 

It has been demonstrated that organotin-mediated multiple carbohydrate esterifications can be controlled by the acytaring reagent and the solvent polarity. When acetyl chloride is used, the reactions are under thermodynamic control, whereas when acetic anhydride is employed, kinetic control takes place. Very good selectivity can furthermore be obtained in more polar solvents. These results can be used in the efficient preparation of prototype carbohydrate structures. 

An analogue of amitriptyline which contains an additional double bond in the central seven membered ring shows much the same activity as the prototype. Treatment of dibenzocycloheptanone 7 with N-bromosuccinimide followed by triethyl amine serves to introduce the additional double bond by the bromination-dehydrohalogenation sequence. Reaction of the carbonyl group with the Grignard reagent from 3-chloropropyl-N,N-dimethyl amine serves to introduce the side chain (73). Acid catalyzed dehydration affords the antidepressant compound cyclobenzaprine (74). ... 

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