Synthetic studies on the indane SHIP1 agonist AQX-1125.

AQX-1125 is an indane based SHIP1 agonist that has been evaluated in the clinic for the treatment of bladder pain syndrome/interstitial cystitis. To support our own studies on SHIP1 agonists as potential treatments for IBD and Crohn's disease, a new synthetic route to the SHIP1 agonist AQX-1125 has been developed. This sequence utilizes a hydroxy-acid intermediate which allows for ready differentiation of the C6 and C7 positions.

Formation of DPM ethers using O-diphenylmethyl trichloroacetimidate under thermal conditions.

Alcohols are effectively converted to their corresponding diphenylmethyl (DPM) ethers by reaction with O-diphenylmethyl trichloroacetimidate in refluxing toluene without the requirement of a catalyst or other additives. A number of acid and base sensitive substrates were protected in excellent yield using this new method without disturbing the pre-existing functionality present in these molecules. This reaction is the first example of the formation of an ether from stoichiometric amounts of a trichloroacetimidate and an alcohol without the addition of a Brønsted or Lewis acid catalyst.