1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 178523895, compound

Temperature

50 °C

A suspension of 4-chloro-N-((3-chloro-5-fluorophenyl)carbamothioyl)benzamide (20.5 g, 59.7 mmol) in TBME (500 mL) was heated to 50° C. 5-(Trifluoromethyl)-1H-pyrazol-3-amine (10.8 g, 71.7 mmol, 1.20 equiv) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC) (17.6 g, 89.6 mmol, 1.50 equiv) were added. The resulting reaction mixture was stirred at 40° C. for 3 hr and then diluted with a saturated aqueous sodium chloride solution (0.5 L). The organic layer of the resulting mixture was isolated, dried (Na2SO4), filtered, and concentrated. The resulting residue was diluted with EtOAc (20 mL), and this mixture was warmed to 50° C., then diluted with heptane (20 mL). Next, the heat source was removed and the mixture was allowed to cool to room temperature, then an ice/water bath was applied to the reaction vessel to affect precipitation. The resulting solids were collected by filtration, rinsed with EtOAc/heptane (1/1 mixture by volume, 20 mL) and air dried at room temperature. Then, the solids were dissolved in EtOH (80 mL) and the resulting mixture warmed to 40° C. EtOH/water (1/1 mixture by volume, 80 mL) was added to the mixture slowly over 40 minutes. Then, the heat source was removed from the reaction vessel and the reaction mixture was allowed to stir at room temperature for 2 days. Then, the reaction mixture was filtered, collected solids were rinsed with EtOH/water (1/1 mixture by volume, 15 mL), and dried (60° C./10 Torr) to afford the title compound (15.2. g, 57% yield). 1H NMR (DMSO-d6) of the title compound: δ 13.3 (s, 1H), 10.7 (s, 1H), 10.0 (s, 1H), 7.90 (s, 1H), 7.90 (d, 2H, J=8.4), 7.72 (d, 1H, J=11.5), 7.63 (m, 3H), 7.07 (d, 1H, J=8.5), 6.00 (s, 1H). HPLC: 98.6% purity at 26.02 min.

1. customThe resulting reaction mixture
2. customThe organic layer of the resulting mixture was isolated
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated
6. additionThe resulting residue was diluted with EtOAc (20 mL)
7. temperaturethis mixture was warmed to 50° C.
8. additiondiluted with heptane (20 mL)
9. customNext, the heat source was removed
10. temperatureto cool to room temperature
11. customan ice/water bath was applied to the reaction vessel
12. customprecipitation
13. filtrationThe resulting solids were collected by filtration
14. washrinsed with EtOAc/heptane (1/1 mixture by volume, 20 mL) and air
15. customdried at room temperature
16. dissolutionThen, the solids were dissolved in EtOH (80 mL)
17. temperaturethe resulting mixture warmed to 40° C
18. additionEtOH/water (1/1 mixture by volume, 80 mL) was added to the mixture slowly over 40 minutes
19. customThen, the heat source was removed from the reaction vessel
20. stirringto stir at room temperature for 2 days
21. filtrationThen, the reaction mixture was filtered
22. customcollected solids
23. washwere rinsed with EtOH/water (1/1 mixture by volume, 15 mL)
24. customdried (60° C./10 Torr)

ORD record

ord-043a7b31173042b1a058da6224056251

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266839B2