Water → (2S,4R)-1-acetyl-6-[3,4-bis(methyloxy)phenyl]-2-methyl-N-3-pyridinyl-1,2,3,4-tetrahydro-4-quinolinamine

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Reaction Steps

To a stirred solution of (2S,4R)-1-acetyl-6-[3,4-bis(methyloxy)phenyl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine (for a preparation see intermediate 94) (50.1 mg, 0.147 mmol) in dichloromethane (DCM) (2 mL) was added triethylamine (0.061 mL, 0.442 mmol) and copper (II) acetate (41.0 mg, 0.226 mmol) followed after 10 min by 3-pyridinylboronic acid (36.4 mg, 0.296 mmol). The resulting mixture was stirred at room temperature for 3 h. Further 3-pyridinylboronic acid (9.1 mg, 0.074 mmol) was added and the mixture was stirred at room temperature for a further 6 days after which time the solvent had evaporated in vacuo. After standing for 19 days, further dichloromethane (DCM) (2 mL) was added followed by further 3-pyridinylboronic acid (18.6 mg, 0.151 mmol) and copper (II) acetate (42.3 mg, 0.233 mmol). The mixture was stirred at room temperature for a further 24 h, then left to stand for 36 h before further triethyalamine (0.061 mL, 0.443 mmol) and 3-pyridinylboronic acid (19.8 mg, 0.161 mmol) were added. Stirring at room temperature continued for a further 6 h before additional 3-pyridinylboronic acid (19.5 mg, 0.159 mmol) was added. After stirring for a further 65 h a 3:1 mixture of water/0.880 ammonia (1 mL) was added and the mixture was stirred for 15 min then was diluted with a saturated NaHCO3 aqueous solution (6 mL). The aqueous phase was extracted with dichloromethane (3×6 mL) and the combined organic phases were dried using a phase separator then concentrated using a stream of nitrogen. The residue was dissolved in methanol (1 mL) and was purified by MDAP (modifier: formic acid) to give (2S,4R)-1-acetyl-6-[3,4-bis(methyloxy)phenyl]-2-methyl-N-3-pyridinyl-1,2,3,4-tetrahydro-4-quinolinamine (2.8 mg, 6.71 μmol, 4.56% yield) as a light brown oil.

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