Reaktion #78319

Reaktionsgleichung

N-methylmorpholine

3-[1-(3-fluoro-2′-methanesulfonyl-biphenyl-4-yl)-2-oxo-piperidin-3-ylamino]-benzonitrile

3-cyanoaniline

Semicarbazide hydrochloride

→

title compound

1-(3-Fluoro-2′-methanesulfonyl-biphenyl-4-yl)-3-[3-(5-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-yl)-phenylamino]-piperidin-2-one

Lösungsmittel

chloroform

MeOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeHCl gas was then bubbled in the mixture for 30 minutes
2. 2
   Sonstigeresulting in a clear solution
3. 3
   SonstigeThe reaction vessel was sealed
4. 4
   EinengenThe mixture was concentrated in vacuo
5. 5
   Sonstigedried
6. 6
   TemperaturThe mixture was refluxed for 48 hours
7. 7
   FiltrationThe precipitate was filtered
8. 8
   Waschenwashed with 1,4-dioxane, water, and ether
9. 9
   SonstigeThe solid was pumped dry

Vorschrift

A sample of 3-[1-(3-fluoro-2′-methanesulfonyl-biphenyl-4-yl)-2-oxo-piperidin-3-ylamino]-benzonitrile, prepared from the compound of Ex. 1, part A and 3-cyanoaniline according to the procedure of Ex. 1, Part B, was suspended in a 2:1 mixture of anhydrous MeOH and chloroform and cooled in a 0° C. ice-bath. HCl gas was then bubbled in the mixture for 30 minutes resulting in a clear solution. The reaction vessel was sealed and stored at 0° C. for 18 hours. The mixture was concentrated in vacuo and dried. The resulting residue was suspended in 1,4-dioxane. Semicarbazide hydrochloride (1.7 eq) was then added, followed by N-methylmorpholine (7.2 eq). The mixture was refluxed for 48 hours. The precipitate was filtered and washed with 1,4-dioxane, water, and ether. The solid was pumped dry to afford the title compound. 1H NMR (DMSO-d6, 300 MHz) δ 11.87 (s, 1H), 11.56 (s, 1H), 8.11(d, J=8.1 Hz, 1H), 7.75 (m, 2H), 7.47 (m, 2H), 7.37 (d, J=11.0 Hz, 1H), 7.29 (d, J=7.9 Hz, 1H), 7.15 (t, J=7.9 Hz, 1H), 7.08 (br m, 1H), 6.96 (d, J=7.3 Hz, 1H), 6.78 (br d, J=9.5 Hz, 1H), 4.28 (m, 1H), 3.73 (t, J=6.2 Hz, 2H), 2.90 (s, 3H), 2.30 (m, 1H), 2.10 (m, 2H), 1.90 (m, 1H); MS ESI (M+H) 522.4.

Quelle