Triethylamine → HCID 178441819, Verbindung

Temperatur

70 °C

To a solution of 5-butyl-3-(6-chlorohex-1-yn-1-yl)-N-(3,4-dimethoxybenzyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine (3.334 g, 7.31 mmol) in anhydrous acetonitrile (4 mL) was added triethylamine (3.06 mL, 21.94 mmol) and pyrrolidine (1.831 mL, 21.94 mmol). The solution was stirred at 70° C. for 18 hours. A further equivalent of pyrrolidine (0.61 mL, 7.31 mmol) and triethylamine (1.019 mL, 7.31 mmol) were added to the reaction mixture. The solution was stirred at 70° C. for a further 3 hours. The cooled reaction mixture was evaporated in-vacuo and the residue partitioned between ethyl acetate and water/brine (1:1). The organic phase was separated, passed through a hydrophobic frit and evaporated in-vacuo to yield a sticky brown gum (4.226 g). The gum was dissolved in the minimum volume of dichloromethane, loaded onto a 340 g silica pre-conditioned cartridge and purified by chromatography using dichloromethane over 1 column volume followed by 0-30% methanol (+1% triethylamine) in dichloromethane gradient over 14 column volumes followed by 30% methanol (+1% triethylamine) in dichloromethane over 3 column volumes. Appropriate fractions were combined and evaporated in-vacuo to yield the title compound as a sticky brown gum (1.838 g).

1. stirringThe solution was stirred at 70° C. for a further 3 hours
2. customThe cooled reaction mixture
3. customwas evaporated in-vacuo
4. customthe residue partitioned between ethyl acetate and water/brine (1:1)
5. customThe organic phase was separated
6. customevaporated in-vacuo

ORD-Eintrag

ord-5557e82b61c8464584c6c01e1c275024

Quelldatensatz

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09173872B2