Water → HCID 67207123, compound

To a stirred solution of methyl 3-[(2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]benzoate (for a preparation see Intermediate 98) (50.0 mg, 0.148 mmol) in dichloromethane (DCM) (2 mL) were added triethyalamine (0.062 mL, 0.443 mmol) and copper (II) acetate (40.2 mg, 0.221 mmol) followed after 10 min by 3-pyridinylboronic acid (36.7 mg, 0.299 mmol). The resulting mixture was stirred at room temperature for 3 h. Further 3-pyridinylboronic acid (9.2 mg, 0.075 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 (18.8 mg, 0.153 mmol) and copper (II) acetate (45.0 mg, 0.248 mmol). The mixture was stirred at room temperature for a further 24 h, then left to stand for 36 h before further triethyalamine (0.062 mL, 0.443 mmol) and 3-pyridinylboronic acid (18.2 mg, 0.148 mmol) were added. The mixture was stirred at room temperature for a further 6 hours before additional 3-pyridinylboronic acid (18.5 mg, 0.151 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). The combined organic phases were dried using a phase separator and the solvent was evaporated under a stream of nitrogen. Purification of the residue by MDAP (modifier: ammonium bicarbonate) gave methyl 3-[(2S,4R)-1-acetyl-2-methyl-4-(3-pyridinylamino)-1,2,3,4-tetrahydro-6-quinolinyl]benzoate (10.1 mg, 0.024 mmol, 16.45% yield) as a clear gum.

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. additionwas added
9. stirringAfter stirring for a further 65 h
10. additionwas added
11. stirringthe mixture was stirred for 15 min
12. extractionThe aqueous phase was extracted with dichloromethane (3×6 mL)
13. customThe combined organic phases were dried
14. customthe solvent was evaporated under a stream of nitrogen
15. customPurification of the residue by MDAP (modifier: ammonium bicarbonate)

ORD record

ord-09744be3d4b743479c41b37c0a652b7a

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08580957B2