6-Chlorooxazolo[4,5-b]pyridin-2(3H)-one

DMF (9 L) was added to a 100 L autoclave.Start the mechanical stirrer and add2, 3-dihydropyrido [2, 3-d] [1, 3] oxazol-2-one(10 kg).The 2, 3-dihydropyrido [2, 3-d] [1, 3] oxazol-2-one was completely dissolved by stirring.N-chlorosuccinimide (12.16 kg)Was dissolved in DMF (30 L).And then slowly dropping N-chlorosuccinimide into the reactor, Control the reaction temperature does not exceed 40 (If necessary, use a circulating condensate pump to cool).After the dropwise addition, the mixture was stirred overnight at room temperature.The reaction was followed by TLC and GC.After completion of the reaction, 39 L of water was slowly added under cooling.The reaction mixture was stirred for 60 minutes and filtered.The filter cake was washed twice with water and dried in vacuo to give a crude product of 11.8 kg. The crude product was recrystallized from dichloromethane and ethyl acetate to give pure product6-chloroxazole [4, 5-b] pyridine-2 (3H) -one(11.1 kg), Yield 89percentTo a solution of oxazolo[4, 5-b]pyridin-2(3H)-one (5.Og, 36.7mmol) was added Nchlorosuccinimide (5.Og, 45.8mmol) at rt. The resulting reaction mixture was stirred at 90 °C for 2h. TLC showed the reaction to be complete. The solvent was removed under reduced pressure and the residue was diluted with H20 (lOOmL) and extracted with EtOAc (3xlOOmL). The organic layer was washed with H20 (lOOmL), dried (Na2504), filtered and concentrated under reduced pressure to 6- chlorooxazolo[4, 5-b]pyridin-2(3H)-one as a brown solid. Yield: 5.Og (55percent); 1H NMR (400 MHz, DMSO-d6): 12.88 (bs, 1H), 8.08 (d, J= 1.8 Hz, 1H), 7.91 (d, J= 1.8 Hz, 1H); MS (ESl+) for CHNOS m/z 170.98 [M+H].Example 6 DMF (9 L) was added to a 100 L autoclave.Start the mechanical stirrer and add2, 3-dihydropyrido [2, 3-d] [1, 3] oxazol-2-one(10 kg).The 2, 3-dihydropyrido [2, 3-d] [1, 3] oxazol-2-one was completely dissolved by stirring.N-chlorosuccinimide (12.16 kg)Was dissolved in DMF (30 L).And then slowly dropping N-chlorosuccinimide into the reactor, Control the reaction temperature does not exceed 40 (If necessary, use a circulating condensate pump to cool).After the dropwise addition, the mixture was stirred overnight at room temperature.The reaction was followed by TLC and GC.After completion of the reaction, 39 L of water was slowly added under cooling.The reaction mixture was stirred for 60 minutes and filtered.The filter cake was washed twice with water and dried in vacuo to give a crude product of 11.8 kg. The crude product was recrystallized from dichloromethane and ethyl acetate to give pure product6-chloroxazole [4, 5-b] pyridine-2 (3H) -one(11.1 kg), Yield 89%DMF was added to a 10L three-neck round bottom flask (2000mL) with reflux condenser on each neck. Oxazole [4, 5-b]pyridine-2(3H)-one (497g) was added with mechanical stirring until it was dissolved. N- chlorosuccinimide (608g) was dissolved in DMF (2500mL). Transferred to a pressure-equalizing dropping funnel, N-chlorosuccinimide was slowly added dropwise to the reaction flask, the reaction temperature is controlled not to exceed 40C (cooling with ice-water if necessary). Afterwhich, the ice bath was removed, then stirred at room temperature overnight. The reaction was monitored by TLC and GC. After completion of the reaction, 4000mL water was slowly added under cooling with ice water. The reaction mixture was stirred for 30 minutes and filtered. The filter cake was washed twice with water and dried under vacuum to give crude 530g. The crude product was recrystallized from ethyl acetate and methylene chloride to give pure product 6-chlorooxazole[4, 5-b]pyridine-2(3H)-one (505g), yield 81%, purity 99.1% (GC) . Melting point 184C ~ 187C (literature 183C ~ 186C).To a solution of oxazolo[4, 5-b]pyridin-2(3H)-one (5.Og, 36.7mmol) was added Nchlorosuccinimide (5.Og, 45.8mmol) at rt. The resulting reaction mixture was stirred at 90 C for 2h. TLC showed the reaction to be complete. The solvent was removed under reduced pressure and the residue was diluted with H20 (lOOmL) and extracted with EtOAc (3xlOOmL). The organic layer was washed with H20 (lOOmL), dried (Na2504), filtered and concentrated under reduced pressure to 6- chlorooxazolo[4, 5-b]pyridin-2(3H)-one as a brown solid. Yield: 5.Og (55%); 1H NMR (400 MHz, DMSO-d6): 12.88 (bs, 1H), 8.08 (d, J= 1.8 Hz, 1H), 7.91 (d, J= 1.8 Hz, 1H); MS (ESl+) for CHNOS m/z 170.98 [M+H].To the solution of 2, 3-dihydropyridino [2, 3-d] [1, 3] azole-2-ketone in DMF (90mL) at 0 was added NCS (12.3g, 91.8mmol) in DMF (50mL) dropwise in 60min. The mixture was warmed to room temperature and react for 3h. To the reacion mixture was added 150mL ice water, and stir for 30min. The solid was collected by filtration to give the desired product (12.0g) .

Molecular Weight:170.55
XLogP3:1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:169.9883050
Monoisotopic Mass:169.9883050
Topological Polar Surface Area:51.2
Heavy Atom Count:11
Complexity:187
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes