Triethylamine → 5-Butyl-3-(5-chloropent-1-yn-1-yl)-N-(2,4-dimethoxybenzyl)-1H-Pyrazolo[4,3-d]pyrimidin-7-amine

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Reaction Steps

Bis(triphenylphosphine)palladium(II)dichloride (101 mg, 0.144 mmol), triethylamine (0.403 mL, 2.89 mmol) and copper iodide (55.0 mg, 0.289 mmol) were added to a nitogen degassed solution of 5-butyl-N-(2,4-dimethoxybenzyl)-3-iodo-1H-pyrazolo[4,3-d]pyrimidin-7-amine (900 mg, 1.926 mmol) in anhydrous N,N-dimethylformamide (23 mL). The mixture was stirred under a nitrogen atmosphere and heated to 60° C. before the addition of 5-chloropent-1-yne (296 mg, 2.89 mmol) in anhydrous N,N-dimethylformamide (2 mL). The reaction was stirred at 60° C. for 3 hours. A further 0.30 equivalents of 5-chloropent-1-yne (59 mg, 0.575 mmol) in anhydrous N,N-dimethylformamide (1 mL) was added to the reaction. The mixture was stirred at 60° C. for a further 2.5 hours and then allowed to cool to room temperature overnight. The reaction mixture was evaporated in-vacuo to yield a brown oil. The resulting oil was partitioned between ethyl acetate (25 mL) and water/brine (1:1, 10 mL). The organic layer was separated, passed through a hydrophobic frit and evaporated in-vacuo to yield a brown oil (1.32 g). The oil was dissolved in the minimum volume of dichloromethane, loaded onto a 100 g silica cartridge and purified by chromatography using a 0-100% ethyl acetate in cyclohexane gradient over 60 minutes. Appropriate fractions were combined and evaporated in-vacuo to yield an orange oil. The oil was dissolved in the minimum volume of dichloromethane, loaded onto a 100 g silica cartridge and re-purified by chromatography using a 0-100% ethyl acetate in cyclohexane gradient over 60 minutes. Appropriate fractions were combined and evaporated in-vacuo to yield the title compound as an orange oil (720 mg).

Provenance & Evidence