.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 4,349,476

« Back to Dashboard

Details for Patent: 4,349,476

Title: Process for producing imidazodiazepines
Abstract:This invention is directed toward pharmacologically active compound of the formula ##STR1## wherein A is ##STR2## R.sub.1 is selected from the group consisting of hydrogen, lower alkyl, hydroxy lower alkyl, acyloxy lower alkyl, phenyl, alkoxy lower alkyl, halo lower alkyl, amino lower alkyl, substituted amino lower alkyl, substituted phenyl, pyridyl, aralkyl and the groups ##STR3## wherein R is hydrogen or lower alkyl and ROOC where R is lower alkyl; R.sub.2 is selected from the group consisting of hydrogen, lower alkyl, hydroxy lower alkyl, acyloxy lower alkyl, alkoxy lower alkyl, halo lower alkyl, amino or substituted amino lower alkyl, amino, cyano, cyano lower alkyl, substituted amino, chloro, bromo and iodo, the group --COOR where R is hydrogen or lower alkyl, the group ##STR4## where R is hydrogen or lower alkyl, or derivatives thereof, e.g., the group R--C.dbd.N--R' wherein R' is hydrogen, lower alkyl, hydroxy, phenyl, alkoxy, amino, mono or di-alkylamino and arylamino and R is hydrogen or lower alkyl, the group ##STR5## (where R and R' are individually hydrogen, lower alkyl, hydroxy lower alkyl, lower alkenyl, aryl or together R and R' form a part of a heterocyclic ring and the group (CH.sub.2).sub.n NRR' where R and R' are hydrogen, lower alkyl, hydroxy lower alkyl, lower alkenyl or together R and R' form a part of a heterocyclic ring and n is 1 to 4); the group ##STR6## where R.sup.10, R.sup.11, R.sup.12 are hydrogen or lower alkyl and the group (CH.sub.2).sub.n NR.sup.13 R.sup.14 where n is 1 to 4 and R.sup.13, R.sup.14 are hydrogen, lower alkyl, hydroxy lower alkyl, lower alkenyl or R.sup.13 and R.sup.14 together form part of a heterocyclic ring, with the limitation that where R.sup.10, R.sup.11 or R.sup.12 is a basic side chain, then the remaining substituents are hydrogen or lower alkyl; R.sub.3 is selected from the group consisting of hydrogen and lower alkyl; R.sub.5 is selected from the group consisting of hydrogen, lower alkanoyloxy and hydroxy; R.sub.4 is selected from the group consisting of hydrogen, halogen, nitro, cyano, trifluoromethyl, lower alkyl, substituted amino, amino, hydroxy lower alkyl and lower alkanoyl; R.sub.6 is selected from the group consisting of phenyl, mono-substituted phenyl, di-substituted phenyl, pyridyl and mono-substituted pyridyl; and ##STR7## is selected from the group consisting of ##STR8## and the pharmaceutically acceptable salts thereof. Also provided are methods for the preparation of these compounds as well as pharmaceutical formulations which contain the active compounds of this invention. The compounds of the formulas illustrated above and their analogs are useful as anticonvulsants, muscle relaxants, anxiolytic and sedative agents.
Inventor(s): Walser; Armin (West Caldwell, NJ), Fryer; Rodney I. (North Caldwell, NJ)
Assignee: Hoffmann-La Roche Inc. (Nutley, NJ)
Filing Date:Mar 12, 1981
Application Number:06/242,946
Claims:1. A process to produce a compound of the formula ##STR94## wherein A is ##STR95## R.sub.1 is selected from the group consisting of hydrogen, lower alkyl, alkoxy lower alkyl, halo lower alkyl; R is hydrogen or lower alkyl; R.sub.3 is selected from the group consisting of hydrogen and lower akyl; R.sub.4 is selected from the group consisting of hydrogen, halogen, cyano, trifluoromethyl, lower alkyl, mono- or di-C.sub.1 to C.sub.7 alkyl or phenyl, chlorophenyl or tolyl substituted amino, amino, hydroxy lower alkyl and lower alkanoyl; R.sub.6 is selected from the group consisting of phenyl, mono-halo or mono-nitro substituted phenyl, di-halo or halo-nitro substituted phenyl, pyridyl and mono-halo or mono-nitro substituted pyridyl; and ##STR96## is selected from the group consisting of ##STR97## which comprises the stepwise reaction of a compound of the formula ##STR98## wherein R.sub.3, R.sub.4, R.sub.6, A and ##STR99## are as above and the leaving group is selected from the group consisting of alkoxides, alkylthio, halo, cyano, phosphate and nitrosoalkylamino

(a) with the anion generated from malonic ester, i.e., a compound of the formula ##STR100## wherein R is lower alkyl; (b) decarboxylating with an alkali metal hydroxide the product of (a);

(c) nitrosating with nitrous acid the product of (b);

(d) reducing with H.sub.2 /Raney nickel or zinc/acetic acid the product of (c);

(e) reacting the product of (d) with an alkanoic acid ortho ester of the formula

wherein R is lower alkyl and R.sub.1 is selected from the group consisting of hydrogen, lower alkyl, alkoxy lower alkyl, halo lower alkyl, to produce the final product as an ester, i.e., R=lower alkyl;

(f) if desired, hydrolysing with alkali metal hydroxides the product of (e) to the final product as as acid, i.e., R=hydrogen.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

How are People Using DrugPatentWatch?

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc