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

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.

1. stirringthe mixture was stirred at room temperature for a further 6 days after which time the solvent
2. customhad evaporated in vacuo
3. waitAfter standing for 19 days
4. additionfurther dichloromethane (DCM) (2 mL) was added
5. stirringThe mixture was stirred at room temperature for a further 24 h
6. waitleft
7. additionwere added
8. stirringStirring at room temperature
9. additionwas added
10. stirringAfter stirring for a further 65 h
11. additionwas added
12. stirringthe mixture was stirred for 15 min
13. extractionThe aqueous phase was extracted with dichloromethane (3×6 mL)
14. customthe combined organic phases were dried
15. concentrationthen concentrated
16. dissolutionThe residue was dissolved in methanol (1 mL)
17. customwas purified by MDAP (modifier: formic acid)

ORD record

ord-4723a1dc1c1a41609ba6d2cf730ea2b6

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08580957B2