Month: July 2012

Reduction of a double bond using NaBH4-Ni in water

Reduction of Undecylinic acid to Undecanoic acid using NaBH4-Ni in water In a 3 Lt four necked round bottom flask equipped with a mechanical stirrer, 250 mL dropping funnel, thermometer and inlet port open to the atmosphere on a water bath was charged under stirring distilled water(1200 mL), sodium hydroxide (88 g, 2.2 mol), undecylinic… Continue reading Reduction of a double bond using NaBH4-Ni in water

IMATINIB

Imatinib Systematic (IUPAC) name 4-[(4-methylpiperazin-1-yl)methyl]-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)benzamideImatinib (originally STI571) is a drug used to treat certain cancers. It is marketed byNovartis as Gleevec (USA) or Glivec (Europe/Australia/Latin America) as its mesylatesalt, imatinib mesilate (INN). Imatinib is the first of a new class of drugs that act by specifically inhibiting a certainenzyme – a receptor tyrosine kinase – that is characteristic of a particular cancer cell, rather than non-specifically inhibiting and killing all rapidly dividing cells. Imatinib… Continue reading IMATINIB

IMATINIB SYNTHESIS

  As an example of research aimed at industrial production one involving imatinib. This cancer drug was one of the first offspring of rational drug design . A group of Northwest University researchers set out to improve the existing Novartis procedure DOI and here is how they did it. 2-acetylpyridine (1) was alkylated with the acetal of N,N-dimethylformamide 2 to enamine 3. A pyrimidine ring in 5was formed with base and reagent guanidine… Continue reading IMATINIB SYNTHESIS

CETRIZINE SYNTHESIS, IN OPRD PAPER

    CETRIZINE BY Reiter, Trinka, Bartha ,Pongo, Volk, Simig DOI Synthetic scale: 50 – 150 Kg Step 1: 4-chlorobenzophenoneorganic reduction (sodium borohydride), methyltrioctylammonium chloride phase-transfer catalyst(toluene/water) Step 2: thionyl chloride chlorination(toluene) Step 3: N-(2-hydroxyethyl)piperazineamine alkylation (toluene) Step 4: free amine liberation NaOHwater/ toluene Step 5: 2-chloro-N,Ndimethylacetamide O-alkylation(toluene), HCl workup Step 6: Amide hydrolysis, NaOH / water Features: single solvent system toluene/water.

ACETYLATION MECHANISM

MECHANISM   In  this reaction an acyl pyridium ion is formed which is the reactive species.  Facile addition of the alcohol to the acyl pyridinium ion regenerates DMAP and, after loss of the oxonium proton to acetate, forms the desired product plus acetic acid which is scavenged by Et3N. reaction—   wt/vol MW moles density equivs. yield… Continue reading ACETYLATION MECHANISM

ARTEMETHER, FIGHT AGAINST MALARIA

ARTEMETHER, FIGHT AGAINST MALARIA Artemether (INN) is an antimalarial for the treatment of multi-drug resistant strains offalciparum malaria. It is combined with Lumefantrine and sold by Novartis under the brand names Riamet and Co-Artem. Bill together with Rodger Stringham and David Teager report on an improved process for the conversion of artemisinin to artemether in Organic Process Research & Development (DOI). step 1 was smooth… Continue reading ARTEMETHER, FIGHT AGAINST MALARIA

The Fráter-Seebach alkylation

The Fráter-Seebach alkylation is the stereoselective alkylation of chiral beta-hydroxy esters using superbases such as LDA or LiHMDS. This organic reaction was first reported by G. Fráter in 1979 (DOI DOI). In the original Fráter publication the starting material is ethyl acetoacetate 1, stereoselectively converted to the beta-hydroxy ester 2 with Baker’s yeast, converted to the dianion 3 with LDA and finally alkylated with iodomethanein HMPA to 4.