Diisopropylethylamine → N-[5-((4aR*,8aS*)-2-amino-4,4a,5,6-tetrahydro-7-oxa-3-thia-1-azanaphthalen-8a-yl)thiophen-3-yl]-5-cyanopyridine-2-carboxamide

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Reaction Steps

5-Cyanopyridine-2-carboxylic acid (19.0 mg), diisopropylethylamine (50.7 μl) and PyBOP (83.5 mg) were sequentially added to a solution of (+)-N,N-di(tert-butyloxycarbonyl)-[(4aR*,8aS*)-8a-(4-aminothiophen-2-yl)-4,4a,5,6,8,8a-hexahydro-7-oxa-3-thia-1-azanaphthalen-2-yl]amine (50 mg) in dichloromethane (5.0 ml) in an ice bath. The mixture was returned to room temperature and stirred overnight. The solvent was evaporated under reduced pressure and the residue was purified by NH-silica gel column chromatography. The resulting intermediate was dissolved in dichloromethane (4.0 ml) and TFA (1.0 ml) was added. After stirring at room temperature for four hours, ice was added to terminate the reaction. The mixture was neutralized with a sodium bicarbonate solution, and the aqueous layer was neutralized with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by NH-silica gel column chromatography to obtain the title compound (33.9 mg).

Provenance & Evidence