Iodoethane → 6-Amino-7-ethyl-2-[3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]-7,9-dihydro-8H-purin-8-one

Participants

Reaction Conditions

Reaction Steps

200 mg (0.392 mmol) of 2-[3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidine-4,5,6-triamine (example 2A) were initially charged in tetrahydrofuran (11.1 ml) and the suspension was cooled to 0° C. Subsequently, 0.43 ml (0.43 mmol) of bis(trimethylsilyl)sodium amide solution (1.0 M in tetrahydrofuran) was added and the mixture was stirred at 0° C. for a further 30 min Thereafter, 31.3 μl (0.392 mmol) of iodoethane were added dropwise and the reaction mixture was stirred at RT overnight. The reaction mixture was cooled again to 0° C. and a further 0.47 ml (0.47 mmol) of bis(trimethylsilyl)sodium amide solution was added. Thereafter, the reaction mixture was stirred at RT overnight and heated to reflux for a further 2 days. Subsequently, the reaction mixture was diluted with ethyl acetate and washed twice with saturated aqueous sodium hydrogencarbonate solution. The organic phase was dried over magnesium sulfate, filtered and concentrated by rotary evaporation. The residue was separated by means of preparative HPLC (eluent: acetonitrile-water with 0.1% formic acid gradient) and the product fractions were concentrated. The crude product was extracted by stirring in methyl tert-butyl ether, and the solids were filtered off and dried under high vacuum. This gave 4.6 mg (2.9% of theory) of the title compound in solid form.

Provenance & Evidence