Pyridines. XI<sup>1</sup> ‐ Acidité Relative Des Hydrogènes Des Méthyles de La S‐Collidine Dans L'Éther Diéthylique et L'Ammoniac Liquide

Compagnon, Paul-Louis; Kimny, Tan; Compagnon, Odette

doi:10.1002/bscb.19840930107

Cited by 2 publications

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“…We were somewhat surprised by just how facile and selective the exchange was, since the acidity of sulfones is low (e.g. CH 3 SO 2 CH 3 p K a =31.1, DMSO solvent)14 and may be similar to the aryl methyl groups (p K a of p ‐tolunitrile is 30.8, DMSO solvent,15 and o ‐tolunitrile has an estimated p K a ∼30, ether solvent16). However, there are many reports of hydrogen–deuterium exchange of sulfones under basic conditions (e.g.…”

Section: Resultsmentioning

confidence: 99%

Unusual base‐catalyzed exchange in the synthesis of deuterated PF‐2413873a

Rozze

Fray

2009

Labelled Comp Radiopharmac

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The preparation of deuterated PF-2413873 (4-[3-cyclopropyl-1-(methanesulfonylmethyl)-5-methyl-1H-pyrazol-4-yl]oxy-2, 6-dimethylbenzonitrile, 1) is described for use as a bioanalytical standard in clinical trials. Two strategies were investigated. The sulfone-containing substituent was labelled by base-catalyzed exchange, but unacceptable deuterium loss was noted under assay conditions. Alternatively, labelling 4-cyano-3,5-dimethylphenol was achieved by heating with deuterium oxide over platinum oxide. After building up the pyrazole ring we discovered that, during the subsequent alkylation to attach the methylthiomethyl group, the base, potassium t-butoxide, caused unwanted scrambling of deuteriums on the aromatic portion and the methylthiomethyl group. Thus, it was necessary to remove all base-labile hydrogens to prevent their exchange. This was accomplished by alkylating the pyrazole with per-deuterated chloromethyl methylsulfide, oxidation to the sulfone, and selective removal of its deuteriums by treatment with sodium hydroxide. The unusual sensitivity and selectivity of these base-promoted exchange reactions are discussed. Thus,

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Section: Resultsmentioning

confidence: 99%

Unusual base‐catalyzed exchange in the synthesis of deuterated PF‐2413873a

Rozze

Fray

2009

Labelled Comp Radiopharmac

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ChemInform Abstract: PYRIDINES. XI. RELATIVE ACIDITY IN DIETHYL ETHER AND LIQUID AMMONIA OF THE HYDROGENS CONTAINED IN THE METHYL GROUPS OF S‐COLLIDINE

Compagnon¹,

Kimny²,

Compagnon³

1984

Chemischer Informationsdienst

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Pyridines. XI¹ ‐ Acidité Relative Des Hydrogènes Des Méthyles de La S‐Collidine Dans L'Éther Diéthylique et L'Ammoniac Liquide

Abstract: The adicity of methyl bonded to pyridine nucleus of the s-collidine depends on the solvent and the counterion nature.

Cited by 2 publications

References 8 publications

Unusual base‐catalyzed exchange in the synthesis of deuterated PF‐2413873a

Unusual base‐catalyzed exchange in the synthesis of deuterated PF‐2413873a

ChemInform Abstract: PYRIDINES. XI. RELATIVE ACIDITY IN DIETHYL ETHER AND LIQUID AMMONIA OF THE HYDROGENS CONTAINED IN THE METHYL GROUPS OF S‐COLLIDINE

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Pyridines. XI1 ‐ Acidité Relative Des Hydrogènes Des Méthyles de La S‐Collidine Dans L'Éther Diéthylique et L'Ammoniac Liquide

Abstract: The adicity of methyl bonded to pyridine nucleus of the s-collidine depends on the solvent and the counterion nature.

Cited by 2 publications

References 8 publications

Unusual base‐catalyzed exchange in the synthesis of deuterated PF‐2413873a

Unusual base‐catalyzed exchange in the synthesis of deuterated PF‐2413873a

ChemInform Abstract: PYRIDINES. XI. RELATIVE ACIDITY IN DIETHYL ETHER AND LIQUID AMMONIA OF THE HYDROGENS CONTAINED IN THE METHYL GROUPS OF S‐COLLIDINE

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Pyridines. XI¹ ‐ Acidité Relative Des Hydrogènes Des Méthyles de La S‐Collidine Dans L'Éther Diéthylique et L'Ammoniac Liquide