تفاعل #424229

معادلة التفاعل

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

المردود 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

المردود 27.6%

المذيبات

N,N-dimethylformamide

ظروف التفاعل

المعالجة

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
   غسيلthe mixture was washed with water and brine
4. 4
   تجفيفThe organic phase was dried (Na2SO4)
5. 5
   ترشيحfiltered
6. 6
   تركيزconcentrated in vacuo
7. 7
   أخرىPurification by preparative HPLC (Gemini column—acetonitrile/0.1% ammonia mobile phase)

الإجراء التجريبي

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).

المصدر