SC-52491

Chemical Name: 4-Amino-N-[1-azatricyclo[3.3.1.0(3,7)]nonan-4(R)-yl]-5-chloro-2-methoxybenzamide
CAS No. 139228-16-3 (stereoisomer), 139344-03-9 (stereoisomer, monoHCl)
项目整合开发状态: Preclinical
项目研究机构: Pfizer (Originator)
合成路线:The Diels-Alder condensation of the fumaric acid (S)-methyl lactate ester (I) with cyclopentadiene (II) gives the norbornene derivative (III),which is submitted to saponification with LiOH and iodolactonization with KI and I2 yielding the iodolactone (IV).The reaction of (IV) with SOCl2 and then with ammonia affords the amide (V).The Hofmann-type rearrangement of (V) by means of hydroxytosyloxy iodobenzene (HTIB) gives the primary amine (VI),which is treated with TsCl and pyridine to yield the sulfonamide (VII).The iodolactone ring is then cleaved with Zn/AcOH affording the norbornene-carboxylic acid (VIII),which is submitted to ozonolysis with O3 to give the dialdehyde (IX).The reduction of (IX) with NaBH4 provides the diol (X),which is cyclized in acidic medium to lactone (XI).The reaction of (XI) with ammonia affords the amide (XII),which is reduced with BH3 to the primary amine (XIII).The protection of (XIII) with 2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile (Boc-ON) gives the carbamate (XIV),which is treated with Ts-Cl to yield the ditosylate (XV).The cyclization of (XV) by means of TFA affords the azanoradamantane sulfonamide (XVI),which is treated with calcium in liquid ammonia to obtain thee corresponding primary amine (XVII).Finally,this compound is condensed with 4-amino-5-chloro-2-methoxybenzoic acid (XVIII) by means of carbonyldiimidazole (CDI) in DMF.