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0 °C

A solution of 5-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine (300 mg, 1 mmol, e.g. which can be as prepared in Intermediate 7) and triethylamine (0.34 ml, 2.5 mmol, 2.5 equivalents) in dichloromethane (20 ml) was stirred and cooled in an ice/water bath under an atmosphere of nitrogen. 4-{4-[(4-Bromobutyl)oxy]butyl}benzoyl chloride (520 mg, 1.5 mmol, 1.5 equivalents, e.g. which can be as prepared in Intermediate 26) was added portion-wise over 2 minutes, and the mixture was stirred at 0° C. for 5 minutes and then at room temperature for 3 hours. Iced water was added to the reaction mixture and the organic phase was separated and collected through a hydrophobic frit. The aqueous phase was extracted with dichloromethane (10 ml), and the organic layers were combined and evaporated to dryness to give a brown oil. The residue was purified by flash chromatography (100 g silica cartridge, FlashMaster II), eluting with a gradient of 0-100% ethyl acetate in cyclohexane over 40 minutes. The fractions containing the product were combined and evaporated to dryness to give the title compound as a glass (0.26 g). LCMS showed MH+=614/616 (Bromine isotope pattern); TRET=3.06 min.

1. temperaturecooled in an ice/water bath under an atmosphere of nitrogen
2. waitat room temperature for 3 hours
3. customthe organic phase was separated
4. customcollected through a hydrophobic frit
5. extractionThe aqueous phase was extracted with dichloromethane (10 ml)
6. customevaporated to dryness
7. customto give a brown oil
8. customThe residue was purified by flash chromatography (100 g silica cartridge, FlashMaster II)
9. washeluting with a gradient of 0-100% ethyl acetate in cyclohexane over 40 minutes
10. additionThe fractions containing the product
11. customevaporated to dryness