合成路线1

The stereospecific synthesis of BCX-1812(RWJ-270201) has been reported: Ring opening of (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (I) with methanolic HCl gives the methyl ester (II), which is N-protected with Boc2O and TEA yielding the carbamate (III). Cyclization of (III) with 2-ethyl-1-nitrobutane (IV) by means of phenyl isocyanate and TEA affords the bicyclic compound (V) and other isomers. Compound (V) is isolated from the mixture and then hydrogenated with H2 over PtO2 in MeOH and a catalytic amount of HCl to provide amine (VI). Reaction of (VI) with acetic anhydride gives the acetamide (VII), which is Boc-deprotected with ethereal HCl yielding amine (VIII). The guanylation of (VIII) with pyrazolecarboxamidine hydrochloride (IX) and DIEA affords the guanidino derivative (X), which is finally hydrolyzed with NaOH to the desired (1S,2S,3R,4R,1'S)-diastereomer.