Nitrogen → methyl 5-{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}-4-methylthiophene-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of (4S,5R)-3-({6-azetidin-1-yl-3-[5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-methoxyphenyl]pyridin-2-yl}methyl)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (27 mg, 0.040 mmol) and methyl 5-bromo-4-methyl-2-thiophene carboxylate (18.74 mg, 0.080 mmol) in THF (0.5 mL) was degassed with N2 at 25° C. 1N K2CO3 (0.5 mL) was added followed by 1,1-bis(di-tert-butylphosphino) ferrocene palladium dichloride (2.60 mg, 3.99 mmol) and the reaction was stirred vigorously at 25° C. under N2 overnight. The reaction was diluted with water and extracted with EtOAc (3×). The combined extracts were dried (Na2SO4) and concentrated in vacuo to afford the crude product. This was purified by preparative TLC (20×20, 1000 μm, hexanes/EtOAc (70/30)) to give methyl 5-{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}-4-methylthiophene-2-carboxylate. LCMS calc.=719.2. found=720.2 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 7.86 (s, 1H); 7.73 (s, br, 2H); 7.62 (s, 1H); 7.47 (d, J=8.6 Hz, 1H); 7.35 (d, J=8.6 Hz, 1H); 7.33-7.23 (m, 1H); 7.03 (d, J=8.6 Hz, 1H); 6.31 (d, J=8.3 Hz, 1H); 5.74-5.31 (m, 1H); 4.87 (d, J=16.2 Hz, 1H); 4.24 (s, br, 1H); 4.23-3.97 (m, 5H); 3.88 (s, 3H); 3.87 (s, 3H); 2.47-2.41 (m, 2H); 2.33 (s, 3H); 0.75-0.53 (m, 3H).

Provenance & Evidence