Potential Inhibitors of Tyrosine Kinase 2: Synthesis of Important Intermediates
Two different synthesis routes towards target molecule 1 have been investigated.
Synthesis route A (see Figure II) is based on previous work by Ragnhild G. Ohm and Cecilie Surdal. This route gave a total yield of 20% for the synthesis of compound 3, in a Z/E-mixture in the ratio 1:0.9. The Z/E-mixture was inseparable by column chromatography (except a small amount of the E-isomer), hence a new synthesis route was contemplated.
Synthesis route B was developed to enable synthesis of enantiomerically pure substrates for use in Suzuki -and Hiyama cross-couplings, towards target molecules (E)-1 and (Z)-1. The first step with condensation between methylpropiolate (18) and arylaldehydes 17a and 17b was accomplished with yields of 46% and 52% respectively (see Figure III).The second step was a protection of propargylic alcohols 16a and 16b with TBDMSCl. This reaction gave yields of 63% and 64% respectively. Subsequent hydrosilylation of the protected 15a to (E)-14a was attempted, but NMR showed unreacted 15a. Attempts on hydrosilylation of compound 16a and 16b gave a complex mixture and no insulatable product.
The Ritter reaction for amidation of the propargylic alcohol 16a was attempted, but 1H NMR showed unreacted starting material.
Place, publisher, year, edition, pages
Institutt for kjemi , 2013. , 107 p.
IdentifiersURN: urn:nbn:no:ntnu:diva-21292Local ID: ntnudaim:8508OAI: oai:DiVA.org:ntnu-21292DiVA: diva2:634811
Gautun, Odd Reidar, FørsteamanuensisMelnes, Silje