Diisopropylethylamine → 1-Amino-6-amino-methylisoquinoline hydrochloride

Participants

Reaction Steps

To a stirred solution of N-tert-butoxycarbonyl-L-proline, Boc-Pro-OH, (6.73 g, 31.25 mmol) in anhydrous N,N-dimethylformamide (100 ml) under an argon atmosphere was added finely ground 1-amino-6-aminomethylisoquinoline hydrochloride (10.0 g, 40.63 mmol) and N,N-diisopropylethylamine (16.17 g, 125.00 mmol). After stirring the slurry for 15 minutes at room temperature 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyl-uronium hexafluorophosphate (17.67 g, 46.88 mmol) was added, portionwise, over 5 minutes, eventually resulting in complete dissolution of the suspended 1-amino-6-amino-methylisoquinoline hydrochloride. The reaction mixture was stirred at room temperature under an argon atmosphere for a further 90 minutes after which time a yellow precipitate of (S)-2-[[[(1-amino-6-isoquinolyl)methyl]amino]carbonyl]-1-pyrrolidine carboxylic acid 1,1-dimethylethyl ester hydrochloride (b) had formed. The precipitate was collected by filtration, washed with dichloromethane (300 ml) until the filtrate was colourless, and then dried under vacuum to give 7.8 g (56%) of title compound (94% pure by HPLC-Luna C18(2) 46×30 mm, gradient, mobile phase acetonitrile:water, 5-100%/4 min, constant 0.1% trifluoroacetic acid). Further product was isolated from the filtrate by evaporating under vacuum to remove dimethylformamide and excess diisopropylethyl amine and adding 500 ml dichloromethane. The resulting precipitate was removed by filtration, washed with dichloromethane (300 ml) and dried under vacuum to give 4.6 g (33%) (91% pure by HPLC-Luna C18(2) 46×30 mm, gradient acetonitrile:water, 5-100%/4 min, constant 0.1% trifluoroacetic acid).

Provenance & Evidence