Acetic Acid → HCID 59458670, compound

Participants

Reaction Steps

To a solution of (R)-1-(3,3-difluorocyclobutyl)-3-(1-(4-fluoro-3-formylphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)urea (20 mg, 0.03 mmol) in MeOH (2 mL) was added NHMe2 (0.009 mL) and a drop of acetic acid. The reaction mixture was stirred at rt for 30 min, followed by addition of NaCNBH3 (2 mg, 0.03 mmol). The reaction mixture was stirred at rt for 1 h. The solvent was removed under reduced pressure and the residue was partitioned between sat. NaHCO3 and EtOAc. The organic phase was concentrated and purified by prep HPLC (Phemomenex Luna 5u C18 Axia column, 21×100 mm, 10%-90% H2O/ACN with 0.1% TFA/, monitoring at 220 nm) to yield (R)-1-(3,3-difluorocyclobutyl)-3-(1-(3-((dimethylamino)methyl)-4-fluorophenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)urea (Example 328, 8 mg, 44% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.28 (d, J=2.27 Hz, 1H), 7.09 (m, 7H), 6.88 (d, J=8.84 Hz, 1H), 6.63 (d, J=7.07 Hz, 2H), 6.51 (br. s., 1H), 5.88 (m, 1H), 4.34 (d, J=12.63 Hz, 1H), 4.10 (m, 2H), 3.87 (m, 1H), 3.31 (d, J=12.63 Hz, 2H), 2.92 (m, 3H), 2.74 (d, J=2.78 Hz, 3H), 2.70 (d, J=3.28 Hz, 3H), 2.46 (m, 2H).

Provenance & Evidence