In doing research on the latest patents on WIPO (28.06.2007), I found a patent from Hoffmann-La Roche describing the synthesis of different isoquinoline aminopyrazoles, this type of molecules are protein kinase inhibitors (Aurora A)(I don't find it on Kinasepro's blog, but maybe I am wrong, otherwise nobody's perfect...).
I present here, only the synthesis of the main nucleus.
Interestingly, this synthesis starts with 1-indanone, which upon the treatment of butylnitrite, furnishes the 2-oxime derivative in 2 hours and in 65% yield (19.5g scale). Then the 2-cyanomethylbenzoic acid is obtained with a Beckmann rearrangement of the oxime previously prepared using the para-toluenesulfonylchloride (Yield = 74%). The reaction of the 2-cyanomethylbenzoic acid and 3-amino-5-pyrazole by a microwave-assisted cyclization in acetic acid in sealed vessel provides the isoquinolone in 75% yield (2g scale). Finally, the chlorination is performed using POCl3 to deliver the 1-chloro-3-aminopyrazolylisoquinoline in 61% yield.
Of course the synthesis continues with either O or S nucleophilic substitution on the chlorine atom or by Suzuki cross-coupling, furthermore different substituents can be introduced on either the pyrazole ring or the phenyl ring of the isoquinoline.
3 commentaires:
Drats, I missed one.
it's a very interesting heterocyclic synthesis but what about the application of such structure to NLO or liquid crystal??? have you ever seen that before?? do you think that a banana shape is possible?? thanks for your kind response
You have good points there, that's why I always love your blog, it looks like you are an expert in this field. keep up the fantastic work, My friend recommends your blog.
My blog:
surendettement rachat credit www.rachatdecredit.net
Enregistrer un commentaire