N-(2-hydroxyethyl)propanamide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride dispersion in oil (˜55%, 72 mg) was added in portions to a well stirred solution of N-(2-hydroxyethyl)propionamide (71 mg, 0.6 mmol) in THF (13 mL). After stirring the mixture for 15 min at RT [6-Chloro-5-(4-chloro-phenyl)-pyridin-3-yl]-((R)-4-isobutyl-2,2-dimethyl-oxazolidin-3-yl)-methanone (225 mg, 0.55 mmol) was added and stirring continued for 6 h at RT. The mixture was poured into water and extracted with diethyl ether. Organic phases were pooled, dried with Na2SO4 and the solvent was evaporated. The residue was purified by column chromatography on silica (cyclohexane/ethyl acetate 8:1) to yield 89 mg of the title compound as a white solid, MS (ISP) 488.2 (M+H)+. was added extracted with diethyl ether dried with Na2SO4 the solvent was evaporated The residue was purified by column chromatography on silica (cyclohexane/ethyl acetate 8:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (4-Chlorophenyl)(2,4-dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanol (100 mg, 0.202 mmol, Example 65), N-(2-hydroxylethyl)propionamide (34.2 μL, 0.303 mmol), toluene (2 mL), and sodium hydride (60% dispersion in mineral oil, 32.3 mg, 0.808 mmol) were combined in a round bottom flask under an N2 atmosphere. The reaction solution was heated to reflux and refluxed overnight. The reaction solution was cooled to room temperature then transferred to a separatory funnel with EtOAc dilution, and extracted with saturated, aqueous NH4Cl then saturated, aqueous NaHCO3 solutions. The organic phase was separated, then dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography (silica gel, 0-10% DCM/MeOH) then via reverse phase chromatography using acetonitrile with 0.05% trifluoroacetic acid in water as eluent. The fractions from the purification containing the desired product were transferred to a separatory funnel with EtOAc and extracted with a saturated, aqueous NaHCO3 solution. The aqueous layer was separated, extracted with EtOAc, then the combined organic phases were dried over MgSO4, filtered and concentrated under reduced pressure to provide the title compound. MS (ESI): mass calcd. for C31H28Cl2N4O3, 574.2; m/z found, 575.2 [M+H]+; 1H NMR (600 MHz, CD3OD) δ ppm 8.14 (s, 1H), 7.83 (d, J=8.8 Hz, 1H), 7.78 (s, 1H), 7.68 (dd, J=8.8, 1.7 Hz, 1H), 7.47-7.41 (m, 2H), 7.41-7.37 (m, 1H), 7.38-7.34 (m, 4H), 7.34-7.30 (m, 2H), 6.32 (s, 1H), 4.52 (t, J=5.6 Hz, 2H), 3.53-3.44 (m, 5H), 2.11 (q, J=7.6 Hz, 2H), 1.04 (t, J=7.6 Hz, 3H). The reaction solution was heated to reflux refluxed overnight extracted with saturated, aqueous NH4Cl The organic phase was separated dried over MgSO4 filtered concentrated under reduced pressure The crude product was purified by flash column chromatography (silica gel, 0-10% DCM/MeOH) The fractions from the purification containing the desired product were transferred to a separatory funnel with EtOAc extracted with a saturated, aqueous NaHCO3 solution The aqueous layer was separated extracted with EtOAc the combined organic phases were dried over MgSO4 filtered concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride dispersion in oil (˜55%, 72 mg) was added in portions to a well stirred solution of N-(2-hydroxyethyl)propionamide (71 mg, 0.6 mmol) in THF (13 mL). After stirring the mixture for 15 min at RT [6-Chloro-5-(4-chloro-phenyl)-pyridin-3-yl]-((R)-4-isobutyl-2,2-dimethyl-oxazolidin-3-yl)-methanone (225 mg, 0.55 mmol) was added and stirring continued for 6 h at RT. The mixture was poured into water and extracted with diethyl ether. Organic phases were pooled, dried with Na2SO4 and the solvent was evaporated. The residue was purified by column chromatography on silica (cyclohexane/ethyl acetate 8:1) to yield 89 mg of the title compound as a white solid, MS (ISP) 488.2 (M+H)+. was added extracted with diethyl ether dried with Na2SO4 the solvent was evaporated The residue was purified by column chromatography on silica (cyclohexane/ethyl acetate 8:1)