Wyeth

American Home Products Corporation

Jean Schmid

Jay Thomas Afragola

Yanzhong Wu

David Michael Blum

Andre A Asselin

William Alvin Kinney

Timothy John Doyle

Jeremy Ian Levin

Semiramis Ayral-Kaloustian

Joseph Zeldis

Arkadiy Zinoviy Rubezhov

Lalitha Krishnan

Asaf Ragim Alimardanov

Marshall A Hayward

Gulnaz Khafizova

Ting-Zhong Wang

Huan-Qiu Li

Mellard Jennings

Zhixin Wen

There is provided a process for the preparation of substituted amino alcohols HO&#x2014;(CH)&#x2014;NRRfrom haloalcohols HO&#x2014;(CH)&#x2014;X, where X is Cl, Br or I, by reaction with an amine HNRR, in water as solvent at a temperature range of about 20&#xb0; C. to about 90&#xb0; C. optionally in the presence of a catalytic amount of an iodide source metal iodides. The haloalcohols are useful in the preparation of 6-[(substituted)phenyl]-triazolopyrimidine compounds which are useful in the treatment of cancer.

Process for preparation of substituted amino alcohols

The invention provides 6-chloro-5-{2,6-difluoro-4-[3-(methylamino)propoxy]phenyl}-2-pyrazin-2-yl-N-[(1S)-2,2,2-trifluoro-1-methylethyl]pyrimidin-4-amine hemifumarate which is a tubulin inhibitor useful in the treatment of cancer and processes of making said hemifumarate.

Tubulin inhibitor and process for its preparation

Methods for preparing substituted phenylsulfonamide compounds of the following structure are provided: or a pharmaceutically acceptable salt thereof, wherein, R-Rare defined herein. wherein, R, m, n, p, r, and s are defined herein.

Methods for preparing sulfonamide compounds

The present invention provides a process for the preparation of 6-[(substituted)phenyl]-triazolopyrimidine dicarboxylic acid salt and as a hydrated salt having the structural formula (I) wherein:

Process for the preparation of tubulin inhibitors

The invention provides 6-chloro-5-{2,6-difluoro-4-[3-(methylamino)propoxy]phenyl}-2-pyrazin-2-yl-N-[(1S)-2,2,2-trifluoro-1-methylethyl]pyrimidin-4-amine hemifumarate which is a tubulin inhibitor useful in the treatment of cancer and processes of making hemifumarate compounds and compositioning of the present invention.

Processes for using a compound of formula III: to make compounds of formulae I and II: and processes for making the compound of formula III, where Rand J are as defined herein.

Method for preparing hydroxamic acids

This invention relates to a process for the preparation of the formula I compound [2-((8,9)-dioxo-2,6-diazabicyclo[5.2.0]-non-1(7)-en-2-yl)ethyl]phosphonic acid, a NMDA antagonist useful as an anticonvulsant and neuroprotectant in situations involving excess release of excitatory amino acids. ##STR1## In the process of the present invention, 3-aminopropyl carbamic acid 1,1-dimethyl-ethyl ester is reacted with a dialkyl vinylphosphonate to obtain N-[3-(t-butyloxycarbonyl-amino)propyl ]-2-aminoethylphosphonic acid dialkyl ester (d) in 80% yield Reaction of (d) with a 3,4-dialkoxycyclobut-3-en-1,2-dione gives [3-[[2-(dialkoxyphosphoryl)ethyl ]-(2-alkoxy-3,4-dioxo-1,2-cyclobuten-1-yl)amino]propyl] carbamic acid 1,1-dimethylethyl ester (e) in 96% yield. Deprotection and cyclization of (e) in trifluoroacetic acid gives [2-((8,9)-dioxo-2,6-diazabicyclo[5.2.0]-non-1(7)-en-2-yl)ethyl]prosphonic acid dialkyl ester (c) in 58% yield. The phosphonic acid diethyl ester (c) was treated with bromotrimethylsilane to give compound I.

Process for the

This invention relates to a process for the preparation of the formula I compound [2-((8,9)-dioxo-2,6-diazabicyclo[5.2.0]-non-1(7)-en-2-yl)ethyl]phosphonic acid, a NMDA antagonist useful as an anticonvulsant and neuroprotectant in situations involving excess release of excitatory amino acids. ##STR1## In the process of the present invention, 3-aminopropyl carbamic acid 1,1-dimethylethyl ester is reacted with a dialkyl vinylphosphonate to obtain N-[3-(t-butyloxycarbonyl-amino)propyl]-2-aminoethylphosphonic acid dialkyl ester (d) in 80% yield. Reaction of (d) with a 3,4-dialkoxycyclobut-3-en-1,2-dione gives [3-[[2-(dialkoxyphosphoryl)ethyl]-(2-alkoxy-3,4-dioxo-1,2-cyclobuten-1-yl) amino]propyl] carbamic acid 1,1-dimethylethyl ester (e) in 96% yield. Deprotection and cyclization of (e) in trifluoroacetic acid gives [2-((8,9)-dioxo-2,6-diazabicyclo[5.2.0]-non-1(7)-en-2-yl)ethyl]phosphonic acid dialkyl ester (c) in 58% yield. The phosphonic acid diethyl ester (c) was treated with bromotrimethylsilane to give compound I.

Process for the preparation of [2-((8.9)-Dioxo-2,6-Diazabicyclo

This invention relates to a process for resolving (.+-.)-cis-1-ethyl-1,3,4,9-tetrahydro-4-(phenylmethyl)pyrano[3,4-b]indole- 1-acetic acid (pemedolac) usinig brucine to obtain the corresponding (1S,4R)-eutomer. Said eutomer is useful as an analgesic.

Resolution of (1S,4R)-1-ethyl-1,3,4,9-tetrahydro-4-(phenylmethyl)

A method for modifying the balance between bone production and bone resorption in a host animal by administration of (-)-N-[[(5-chloro-benzothiazolyl)-thio]phenylacetyl]-L-cysteine to inhibit bone loss.

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Chester, NY, United States of America

Jean Schmid