Reaktion #424229

Reaktionsgleichung

Ethyl acetate

N-(2-chloroethyl)-pyrrolidine hydrochloride

cesium carbonate

N-cyclopropyl-3-(3-(2-(2-hydroxyphenyl)propan-2-ylamino)-2-oxopyrazin-1(2H)-yl)-4-methylbenzamide

N-Cyclopropyl-3-[3-[[1-(2-hydroxyphenyl)-1-methylethyl]amino]-2-oxo-1(2H)-pyrazinyl]-4-methyl-benzamide

N-(2-chloroethyl)-pyrrolidine, hydrochloride

cesium carbonate

→

title compound

Ausbeute 27.6%

N-Cyclopropyl-4-methyl-3-[3-[[1-methyl-1-[2-[2-(1-pyrrolidinyl)ethoxy]phenyl]ethyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzamide

Ausbeute 27.6%

Lösungsmittel

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe reaction mixture was stirred at 100° C. for 10 h
2. 2
   workup.WAITat 90° C. for 10 h
3. 3
   Waschenthe mixture was washed with water and brine
4. 4
   TrocknenThe organic phase was dried (Na2SO4)
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated in vacuo
7. 7
   SonstigePurification by preparative HPLC (Gemini column—acetonitrile/0.1% ammonia mobile phase)

Vorschrift

To a stirred solution of N-cyclopropyl-3-(3-(2-(2-hydroxyphenyl)propan-2-ylamino)-2-oxopyrazin-1(2H)-yl)-4-methylbenzamide (Example 134, 0.1 g) in N,N-dimethylformamide (3 mL), N-(2-chloroethyl)-pyrrolidine, hydrochloride (0.12 g) and cesium carbonate (0.47 g) were added. The reaction was stirred under nitrogen at 80° C. for 12 h. After 2 h additional batches of N-(2-chloroethyl)-pyrrolidine hydrochloride (0.12 g) and cesium carbonate (0.47 g) were added. The reaction mixture was stirred at 100° C. for 10 h and then at 90° C. for 10 h. Ethyl acetate was added and the mixture was washed with water and brine. The organic phase was dried (Na2SO4), filtered and concentrated in vacuo. Purification by preparative HPLC (Gemini column—acetonitrile/0.1% ammonia mobile phase) afforded the title compound as a solid (34 mg).

Quelle