(+)-(1S,3R)-N-BOC-3-AMINOCYCLOPENTANECARBOXYLIC ACID

white powder

A half-dram vial was charged with (lR, 3S)-3-((tert- butoxycarbonyl)amino)cyclopentane-l-carboxylic acid (0.2 M in 1, 4-dioxane, 225 mu., 45 muiotaetaomicron), 5-phenylthiazol-2-amine (0.2 M in 1, 4-dioxane, 225 mu, , 45 muiotaetaomicron) and DIEA (30 mu, , neat, 172 mupiiotaomicron), then a solution of 2-chloro-l, 3-dimethylimidazolinium chloride (0.2 M in DCE, 275 mu^, 55 mupiiotaomicron) was added. The vial was sealed and shaken at room temperature for 16 h. The reaction mixture was diluted with brine (500 mu.) and extracted with ethyl acetate (2 x 500 mu.). The combined organic layers were evaporated to dryness under a stream of N2 and 1, 4-dioxane (250 mu, ) was added to the residue. The vial was sealed and shaken at 50 °C for 15 min to dissolve the residue, then cooled to room temperature. HCI (4 M in 1, 4-dioxane, 150 mu., 600 muiotaetaomicron) was added, the vial was sealed and shaken at room temperature for 3 h. The solvent was evaporated and DMA (200 mu.) and DIEA (50 mu., neat, 287 muiotaetaomicron) were added. The vial was sealed and shaken at 50 °C for 15 min to dissolve the residue, then cooled to room temperature. Cyanogen bromide (0.4 M in DMA, 225 mu., 90 muiotaetaomicron) was added, the vial was sealed and shaken at room temperature for 3h. DMSO (300 mu.) and AcOH (45 mu.) were added and the mixture was purified by mass triggered preparative HPLC. The product-containing fractions were combined and concentrated in a Genevac to afford (lR, 3S)-3-(cyanoamino)-N-(5-phenyl-l, 3-thiazol-2-yl)cyclopentane-l- carboxamide as an off-white solid. LC-MS (ESI) m/z 313 [M+H]+