American Cyanamid Company

Wyeth Holdings Corporation

Bison-werke Bahre & Greten Gmbh & Co Kg

Thurairajah Padmanathan

Panolil C Raveendranath

Bogdan Kazimierz Wilk

Sreenivasulu Megati

Yanzhong Wu

Kenneth E Green

Joseph D'Antuono, Iii

Constantine Gletsos

John Thomas Kendall

John L Considine, Jr

The invention is a process for the preparation of compounds of the Formula I:where R, R, R, Rand Rare defined in the specification, which are intermediates useful for the preparation of tubulin inhibitors which are useful in the treatment of cancer.

Process for the synthesis of intermediates useful for the synthesis of tubulin inhibitors

The invention is a process improvement for producing N-�3-(3-cyano-pyrazolo�1,5-a!pyrimidin-7-yl)phenyl!-N-ethyl-acetamide which is useful as an anxiolytic, antiepileptic, sedative-hypnotic agent and skeletal muscle relaxant. The disclosed invention comprises reacting 3-dimethylamino-1-(3-N-ethyl-N-acetyl-aminophenyl)-2-propen-1-one or a suitable salt thereof with 3-aminopyrazole-4-carbonitrile or a suitable salt thereof in a mixture comprising water and acetic acid or a suitable salt thereof, rather than in acetic acid alone.

Process improvement in the synthesis of

An improved process for the preparation of 2' and 3'-(halo-substituted)-2',3'-dideoxy nucleosides by reacting a protected anhydrothymidine compound with a halogenating composition containing a substituted organoaluminum compound which exhibits greater solubility in conventional solvents than AlF.sub.3.

Process for the preparation of deoxynucleosides

This invention provides a process for preparing a 2-hydrazino-1,3-diazacycloalk-2-ene hydrohalide. The process comprises reacting a one molar proportion of either tautomeric isomer of a 2-nitroamino-1,3-diazacycloalk-2-ene represented by the following formulas: ##STR1## wherein R.sup.1 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 hydroxyalkyl, C.sub.1 -C.sub.6 alkoxyalkyl, phenyl, substituted phenyl, benzyl, or substituted benzyl, R.sup.2 and R.sup.3 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkoxyalkyl, hydroxyl, aryl, substituted aryl, aralkyl and substituted aralkyl, and n is an integer from 0 to 3 with about an equimolar proportion of an ammonium halide or hydrazonium halide, and about a 1 to 2 molar proportion of hydrazine hydrate in a composition selected from a C.sub.1 to C.sub.4 aliphatic alcohol, water or a mixture thereof, at a temperature from about ambient to the reflux, and isolating the end product as a monohydrohalide. This invention also provides a process for preparing a 2-hydrazino-1,3-diazacycloalk-2-ene dihydrohalide. The process comprises reacting a compound of the formula: ##STR2## wherein R.sup.1 is hydrogen, C.sub.1 to C.sub.6 alkyl, or C.sub.1 to C.sub.6 hydroxyalkyl, R.sup.2 and R.sup.3 are independently hydrogen or C.sub.1 to C.sub.6 alkyl, n is 0 to 3 and X is a halide ion, with hydrogen halide wherein the halide ion is the same as defined above in a C.sub.1 to C.sub.4 alkyl alcohol at about 0.degree. to 30.degree. C.; and recovering the corresponding 2-hydrazino-1,3-diazacycloalk-2-ene dihydrohalide.

Process for preparing 2-hydrazino-1,3-diazacycloalk-2-ene hydrohalides

1-Nitroanthraquinone is produced in highly pure form by a process comprising the steps of: partially oxidizing 3-nitro-o-xylene (I) to 2-methyl-3-nitrobenzoic acid (II) converting II to 2-methyl-3-nitrobenzoyl halide (III), converting III to the novel intermediate 2-methyl-3-nitrobenzophenone (IV), oxidizing IV to 2-benzoyl-6-nitrobenzoic acid (V) and cyclizing V to 1-nitroanthraquinone.

2-Methyl-3-nitrobenzophenone

1-Nitroanthraquinone is produced in highly pure form by a process comprising the steps of partially oxidizing 3-nitro-o-xylene (I) to 2-methyl-3-nitrobenzoic acid (II) converting II to 2-methyl-3-nitrobenzoyl halide (III), converting III to the novel intermediate 2-methyl-3-nitrobenzophenone (IV), oxidizing IV to 2-benzoyl-6-nitrobenzoic acid (V) and cyclizing V to 1-nitroanthraquinone.

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Piscataway, NJ, United States of America

Thurairajah Padmanathan