Dimethylformamide → 3-{3-[6-azetidin-1-yl-2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl]-4-methoxyphenyl}propanamide

Participants

Reaction Steps

To a solution of 3-{3-[6-Azetidin-1-yl-2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl]-4-methoxyphenyl}propanoic acid (EXAMPLE 60) (66 mg, 0.104 mmol) in DCM (4 ml) was added oxalyl chloride (2M in DCM) (0.259 ml, 0.518 mmol) and a drop of DMF. The solution was stirred for 20 minutes, concentrated, dissolved in THF (3 ml), added ammonium hydroxide (0.144 ml, 1.035 mmol) and stirred overnight. The crude was concentrated, dissolved in MeOH, filtered and purified by RP HPLC to afford 38 mg (0.060 mmol) of 3-{3-[6-azetidin-1-yl-2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl]-4-methoxyphenyl}propanamide. This was combined with N,N-dimethylformamide dimethyl acetal (1 ml, 7.50 mmol) and heated at 120° C. for 40 minutes. The reaction mixture was concentrated, added AcOH (1 ml), hydrazine hydrate (7.26 μl, 0.119 mmol) and heated at 90° C. for 1.5 hours. Added saturated aqueous sodium hydrogen carbonate to the reaction mixture and extracted 3 times with ethyl acetate. The combined organics were washed with brine, dried over sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by TLC and RP HPLC and lyophilized from MeCN/water to afford the title compound. Mass spectrum (ESI) 661.3 (M+1). 1H NMR (500 MHz, CD3OD): δ 8.07 (br s, 1H); 7.97 (s, 1H); 7.89 (s, 2H); 7.25 (d, J=8.3 Hz, 1H); 7.14 (d, J=8.4 Hz, 1H); 6.94 (d, J=8.4 Hz, 1H); 6.89 (s, 1H); 6.34 (d, J=8.3 Hz, 1H); 5.76 (s, 1H); 4.57 (m, 1H); 4.24 (m, 1H); 4.05 (t, J=7.4 Hz, 4H); 3.92 (m, 1H); 3.73 (s, 3H); 3.03 (d, J=14.7 Hz, 4H); 2.45-2.37 (m, 2H); 0.60 (s, 3H).

Provenance & Evidence