Methyl 8-[bis-(tert-butoxycarbonyl)amino]-pyrazolo[5,1-a]isoquinoline-7-carboxylate → Methyl 8-[bis-(tert-butoxycarbonyl)amino]-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate

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Reaction Steps

A solution of methyl 8-[bis-(tert-butoxycarbonyl)amino]-pyrazolo[5,1-a]isoquinoline-7-carboxylate (Intermediate 7, 0.36 g) in dioxane was passed through the H-Cube, using a 20% palladium hydroxide on carbon cartridge, eluting at 0.5 mL/minute, at 100° C. and 100 bar. Two fractions were isolated. The first fraction was concentrated in vacuo to give methyl 8-[bis-(tert-butoxycarbonyl)amino]-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate (0.044 g). The second fraction, containing the starting material was concentrated in vacuo then dissolved in a mixture of acetic acid in dioxane solution (20%, 40 mL) and was passed through the H-Cube®, using a 20% palladium hydroxide on carbon cartridge, eluting at 1 mL/minute, at 95° C. and 100 bar. The eluent was concentrated in vacuo and the residue purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-80% to give a solid which was combined with the earlier product to give a 3:7 mixture of methyl 8-[bis-(tert-butoxycarbonyl)amino]-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate and methyl 8-tert-butoxycarbonylamino-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate (0.084 g).

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