Dimethylformamide → Quinoline

Oxalyl chloride (8.15 mL) is added dropwise to the cold mixture (10±5° C.) of Thiazole acid 8 (20.18 g) is dissolved in THF (300 mL) and DMF (300 μL) over a period of ˜5 min keeping the internal temperature at 10±5° C. The reaction mixture becomes yellow and homogenous. The cooling bath is removed and the mixture is allowed to reach ambient temperature over a period of ˜30 min. Gas evolution is observed. The mixture is stirred at ambient temperature for 30 min to 1 hour. A solution of aniline 7 (19.8 g), DMAP (140 mg) and THF (35 mL) was added at 10±5° C. Et3N (13.2 mL) was added in portions at 10±5° C. over a period of 10 min. The ice bath was removed and mixture was heated to 65±2° C. and stirred overnight (18 h). The mixture was allowed to reach ambient temperature, diluted with EtOAc (150 mL) and washed with water (150 mL). NaHCO3 (5%, 225 mL) was added to the organic portion and the mixture was stirred at ambient temperature for 30 min. The organic portion was concentrated under reduced pressure at approx. 40° C. EtOAc (150 mL) was added to the resulting material and the residual water was removed and the mixture was concentrated under reduced pressure at approx. 40° C. (to azeotrope water). EtOAc (94 mL) was added and the resulting slurry was stirred for 2-6 h and filtered. The solid was washed with EtOAc (30 mL) followed by heptane (30 mL) and air dried for 1 h to give the desired product in 70% yield.

1. customat 10±5° C
2. customThe cooling bath is removed
3. additionA solution of aniline 7 (19.8 g), DMAP (140 mg) and THF (35 mL) was added at 10±5° C
4. additionEt3N (13.2 mL) was added in portions at 10±5° C. over a period of 10 min
5. customThe ice bath was removed
6. temperaturemixture was heated to 65±2° C.
7. stirringstirred overnight (18 h)
8. customto reach ambient temperature
9. additiondiluted with EtOAc (150 mL)
10. washwashed with water (150 mL)
11. additionNaHCO3 (5%, 225 mL) was added to the organic portion
12. stirringthe mixture was stirred at ambient temperature for 30 min
13. concentrationThe organic portion was concentrated under reduced pressure at approx. 40° C
14. additionEtOAc (150 mL) was added to the resulting material
15. customthe residual water was removed
16. concentrationthe mixture was concentrated under reduced pressure at approx. 40° C. (to azeotrope water)
17. additionEtOAc (94 mL) was added
18. stirringthe resulting slurry was stirred for 2-6 h
19. filtrationfiltered
20. washThe solid was washed with EtOAc (30 mL)
21. customdried for 1 h

ORD record

ord-e42d252c8b4e4818aa043dcc5fb8b6f6

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362035B2