Ethanol → HCID 117667266, compound

Temperature

50 °C

A mixture of 6-bromo-4,4-difluoro-1,2,3,4-tetrahydro-[1,8]naphthyridine (86.2 mg, 0.35 mmol) and benzoyl isocyanate (85.9 mg, 0.51 mmol, 90%) in 5 mL CH2Cl2 is heated at 50° C. for 2 hrs. The mixture is concentrated the dryness. The residue is dissolved into 5 mL of EtOH, K2CO3 (81.2 mg, 0.59 mmol) is added and the mixture is heated at 50° C. for 2 h. The mixture is concentrated to dryness. The residue is dissolved into 20 ml of H2O and neutralized by the addition of AcOH. This is extracted with 60 mL EtOAc, washed with 2×20 mL of H2O and 1×20 mL of brine. The organic phase is dried with MgSO4, filtered and concentrated. The residue is applied to a silica preparative TLC plate and eluted (75% EtOAc/hexanes) to give 89.6 mg of 6-bromo-4,4-difluoro-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amide

1. concentrationThe mixture is concentrated the dryness
2. additionis added
3. temperaturethe mixture is heated at 50° C. for 2 h
4. concentrationThe mixture is concentrated to dryness
5. dissolutionThe residue is dissolved into 20 ml of H2O
6. additionneutralized by the addition of AcOH
7. extractionThis is extracted with 60 mL EtOAc
8. washwashed with 2×20 mL of H2O and 1×20 mL of brine
9. dry with materialThe organic phase is dried with MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. washeluted (75% EtOAc/hexanes)

ORD record

ord-7b1432a2a81647daab5fec6e821d164b

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181272B2