聚(苯乙烯-二乙烯苯) → 6-benzylamino-3,4-dihydro-2H-isoquinolin-1-one

温度

130 °C

In a 5 mL sealed MW* test tube was 6-bromo-3,4-dihydroisoquinolin-1(2H)-one (50 mg, 0.22 mmol), phenylmethanamine (97 µl, 0.88 mmol), BINAP (6.89 mg, 0.01 mmol) and palladium(II) acetate (2.483 mg, 0.01 mmol) in DMF (500 mL) combined to give a tan suspension. potassium tert-butoxide (24.82 mg, 0.22 mmol) was then added last. Placed test tube onto Smith MW* platform. Heated reaction to 130°C for 4 minutes. Reaction know has a heavy black ppt present. Took LCMS - there is some product (~15%) beginning to form. Placed sealed test tube in heated (130°C) oil bath overnight. Took LCMS - all SM is consumed with a moderate product peak in evidence. Transferred reaction to separatory funnel. Partitioned reaction with EtOAc (40 ml) and water (25 ml). Separated off aq layer. Washed with sat NaCl. The organic was dried MgSO4, filt and conc - pale yellow syrup, 02915-84-0. Dissolved sample in 100% MeOH, added 2 drops NH4OH to adjust pH of sample and filtered off insolubles. The residue was purified via Agilent prep HPLC: Gradient run of 20-95% MeOH/H2O with 10 mmol NH4CO3 buffer (pH 10) over 25 mins. Flow rate 40 ml/min at wavelength 220 nM collection. 250 X 21.2 mm Gemini Axia pakC18 10 micron column. Collected like fractions which were concentrated under pump vacuum. Yield is low but see a mixture of products by NMR. Spectra shows desired material plus dialkylation product. Will reset and scale up reaction but lower amount of benzylamine and try the MW* only.

ORD记录

ord-59e34daf62ce45d3ab308432983c78e6

来源数据集

750 AstraZeneca ELN dataset

原始链接

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