Diisopropylethylamine → 9H-9-fluorenylmethyl N-{2-[3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidino]-1,1-dimethyl-2-oxoethyl}-N-methylcarbamate

Participants

Reaction Steps

A mixture of 3-iodo-1-(3-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine dihydrochloride (0.17 g, 0.00042 mol), 2-[[(9H-9-fluorenylmethoxy)carbonyl]-(methyl)amino]-2-methylpropanoic acid (0.175 g, 0.00052 mol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.1 g, 0.00052 mol), N,N-diisopropylethylamine (0.23 g, 0.0018 mol) and 1-hydroxy-7-azabenzotriazole (0.057 g, 0.00042 mol) in anhydrous dichloromethane (7 mL) was stirred for 18 hours at room temperature. Additional 2-[[(9H-9-fluorenylmethoxy)carbonyl](methyl)amino]-2-methylpropanoic acid (0.044 g, 0.00013 mol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.025 g, 0.00013 mol) were added to the reaction and stirred for 16 hours. The solvent was removed under reduced pressure. The residue was partitioned between brine and ethyl acetate. The aqueous layer was extracted with ethyl acetate, and the combined organic solvent was removed under reduced pressure, and the residue was purified by RP-HPLC (Hypersilprep HS C18, 8 μm, 250×21.1 mm; 5%-100% over 20 min with 0.1 M ammonium acetate, 21 mL/min) to yield 9H-9-fluorenylmethyl N-{2-[3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidino]-1,1-dimethyl-2-oxoethyl}-N-methylcarbamate (0.030 g, 0.00005 mol). RP-HPLC (Delta Pak C18, 5 μm, 300A, 15 cm; 5%-85% acetonitrile—0.1M ammonium acetate over 10 min, 1 mL/min) Rt 11.2 min. MS: MH+ 666

Provenance & Evidence