1,3-DIHYDRO-2H-IMIDAZO[4,5-C]PYRIDIN-2-ONE

PREPARATION 6 Preparation of 2(1H, 3H)-oxo-imidazo[4, 5-c]-pyridine A mixture of 3 g of 3, 4-diaminopyridine, 1.65 g of urea, and 30 ml of N, N-dimethylformamide was heated to reflux for 6 hours. The reaction mixture was cooled to room temperature and stirred for 12 hours. The precipitated solids were collected by filtration and dissolved in 30 ml of methanol. The resultant solution was treated with active carbon and evaporated under reduced pressure to give 3.1 g of the title compound as a white solid. m.p 315 C. (decomp.) IR (KBr, cm-1): 3125; 1717; 1630. NMR (DMSO-d6) 8.14(1H, s); 8 10(1H, d, J=5.19Hz); 6.97 (1H, d, J=5.19Hz).PREPARATION 3 2-(1H, 3H)-Oxo-imidazo[4, 5-c]pyridine 3 G of 3, 4odiaminopyridine and 1.65 g of urea were added to 30 ml of dimethylformamide. The mixture was stirred under reflux for 6 hrs, allowed to cool to room temperature, and stirred further for 12 hrs to precipitate solids. The resulting solids were filtered out, and dissolved in methyl alcohol. The resulting solution was treated with active carbon, and concentrated under reduced pressure to give 3.1 g of the title compound as a white solid. IR (KBr, cm-1): 3125; 1717; 1630. NMR (DMSO-d6): 8.14(1H, s); 8.10(1H, d); 6.97(1H, d).To a vial charged with (S)-3-(4-bromophenyl)-5, 5-dimethyl-4- phenyloxazolidin-2-one (0.100 mg, 0.289 muetaiotaomicron), potassium carbonate (0.120 mg, 0.867 muetaiotaomicron), copper (I) iodide (0.055 mg, 0.289 muetaiotaomicron), and lH-imidazo[4, 5-c]pyridin-2(3H)- one (commercially available from Prime Organics Inc. Woburn, MA) (1 17 mg, 0.867 muetaiotaomicron) were added n-butanol (1.155 mu.) and N N2-dimethylethane-l, 2-diamine (0.051 mg, 0.578 muetaiotaomicron). The suspension was purged with nitrogen, and then sealed and shaken overnight at 1 10C. The resulting suspension was cooled to room temperature and filtered through Celite brand filter aid. The filtrate was dried under reduced pressure and the residue was dissolved in DMSO and purified using RP-HPLC ramping ACN in H20 (10 - 90%, 0.1% TFA throughout). Separation of isomers was accomplished and the respective product containing eluents were dried under reduced pressure providing products which were lyophilized from MeOH/H20 providing (S)- 5, 5-dimethyl-3-(4-(2-oxo-lH-imidazo[4, 5-c]pyridin-3(2H)-yl)phenyl)-4- phenyloxazolidin-2-one (5 mg, 4%) as a yellow solid and (S)-5, 5-dimethyl-3-(4-(2-oxo- 2, 3-dihydro- lH-imidazo[4, 5-c]pyridin- 1 -yl)phenyl)-4-phenyloxazolidin-2-one (5 mg, 4%) as a light brown solid. Structures were assigned arbitrarily. Data for product A: lH NMR (500 MHz, DMSO-d6) delta = 8.22 (d, J= 5.2 Hz, 1 H), 8.14 (s, 1 H), 7.69 - 7.64 (m, 2 H), 7.51 (d, J= 9.0 Hz, 2 H), 7.42 - 7.38 (m, 2 H), 7.35 - 7.28 (m, 3 H), 7.12 (d, J = 5.2 Hz, 1 H), 5.51 (s, 1 H), 1.66 (s, 3 H), 0.93 (s, 3 H). m/z (ESI) 401.2 (M+H)+. Data for product B: FontWeight='Bold' FontSize='10' H NMR (500 MHz , DMSO-d6) delta = 8.29 (s, 1 H), 8.18 (s, 1 H), 7.67 (d, J= 9.0 Hz, 2 H), 7.47 (d, J= 8.9 Hz, 2 H), 7.42 - 7.38 (m, 2 H), 7.35 - 7.28 (m, 3 H), 6.99 (d, J= 5.4 Hz, 1 H), 5.51 (s, 1 H), 1.66 (s, 3 H), 0.93 (s, 3 H). m/z (ESI) 401.2 (M+H)+.