[14C]-labelling of benzisothiazolone based inhibitors of human leukocyte elastase

The [C-14] labelled synthesis of two benzisothiazolone based inhibitors of Human Leukocyte Elastase is described. These are [3-C-14]-[6-methoxy-4-(1-methylethyl)-1,1,3-trioxo-1, 2-benzisothiazol-2(2H)-yl]methyl [carboxy-C-14]-2,6-dichlorobenzoate, [C-14(2)]-WIN 63394, 2, and [3-C-14]-[6-methoxy-4-(1-methylethyl)-1,1,3-trioxo-1, 2-benzisothiazol-2(2H)-yl]methyl [carboxy-C-14]-2,6-dichloro-3-[(2-pyrrolidin-1 -yl)ethoxy]benzoate hydrochioride, [C-14(2)]-WIN 64733, 3. The synthesis of the intermediate [3-C-14]-2-(chloromethyl)-6-methoxy-4-(1-methylethyl)-1, 2-benzisothiazol-3(2H)-one 1,1-dioxide, 8, common to both these syntheses, was achieved in 8 steps in 37% radiochemical yield.