Dimethylformamide → HCID 117652589, compound

To a mixture of N-[(5-chloro-2-oxo-1,3-benzothiazol-3(2H)-yl)acetyl]-N-methylglycine (205 mg) and THF (5 mL) were added oxalyl chloride (78 μL) and a catalytic amount of DMF under ice-cooling, followed by stirring at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure. A mixture of the residue and dichloromethane (4 mL) was added to a mixture of 2-amino-4-chlorophenol (84 mg), TEA (91 μL), and dichloromethane (1 mL) under ice-cooling, followed by stirring at room temperature overnight. The reaction mixture was added to brine, followed by extraction with chloroform. The organic layer was dried over Na2SO4 and then concentrated under reduced pressure. To a mixture of the residue and toluene (5 mL) was added p-toluenesulfonic acid monohydrate (134 mg), followed by heating to reflux for 5 hours. The reaction mixture was cooled to room temperature, diluted with EtOAc, and washed with water, a saturated aqueous NaHCO3 solution, and brine in this order. The organic layer was dried over Na2SO4 and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: Hex/EtOAc=85/15-50/50). To the purified product thus obtained was added diethyl ether. The resulting solid was collected by filtration and then washed with diethyl ether to obtain N-[(5-chloro-1,3-benzoxazol-2-yl)methyl]-2-(5-chloro-2-oxo-1,3-benzothiazol-3(2H)-yl)-N-methylacetamide (59 mg).

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. additionA mixture of the residue and dichloromethane (4 mL)
3. additionwas added to a mixture of 2-amino-4-chlorophenol (84 mg), TEA (91 μL), and dichloromethane (1 mL) under ice-
4. temperaturecooling
5. stirringby stirring at room temperature overnight
6. additionThe reaction mixture was added to brine
7. extractionfollowed by extraction with chloroform
8. dry with materialThe organic layer was dried over Na2SO4
9. concentrationconcentrated under reduced pressure
10. additionTo a mixture of the residue and toluene (5 mL)
11. additionwas added p-toluenesulfonic acid monohydrate (134 mg)
12. temperatureby heating
13. temperatureto reflux for 5 hours
14. temperatureThe reaction mixture was cooled to room temperature
15. additiondiluted with EtOAc
16. washwashed with water
17. dry with materialThe organic layer was dried over Na2SO4
18. concentrationconcentrated under reduced pressure
19. customThe residue was purified by silica gel column chromatography (eluent: Hex/EtOAc=85/15-50/50)
20. customTo the purified product thus obtained
21. filtrationThe resulting solid was collected by filtration
22. washwashed with diethyl ether

ORD record

ord-0e1998317fa24e08a75e3f66b4c3b9e4

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08937087B2