تفاعل #424227

معادلة التفاعل

1-(2-chloroethyl)-pyrrolidine hydrochloride

cesium carbonate

3-(3,5-dibromo-2-oxo-2H-pyrazin-1-yl)-4-methyl-benzoic acid, methyl ester

4-(2-aminoethyl)-phenol

triethylamine

→

title compound

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

المذيبات

N,N-dimethylformamide

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe reaction mixture was cooled to room temperature
2. 2
   أخرىquenched with sat. NaHCO3
3. 3
   استخلاصThe mixture was extracted with dichloromethane
4. 4
   غسيلThe pooled organics were washed with water and brine
5. 5
   تجفيفdried (Na2SO4)
6. 6
   ترشيحfiltered
7. 7
   أخرىthe solvent removed
8. 8
   workup.ADDITIONfollowed by the addition of cyclopropylamine (0.15 mL) and cyclopentylmagnesium bromide (2M in diethyl ether, 0.75 mL) portionwise
9. 9
   workup.STIRRINGThe reaction mixture was stirred under nitrogen for 1 h before the addition of ethanol (2 mL), ammonium formate (300 mg) and 10% palladium on carbon (30 mg)
10. 10
    درجة الحرارةThe reaction mixture was heated within a microwave at 100° C. for 60 minutes
11. 11
    ترشيحfiltered
12. 12
    غسيلwashed with ethanol
13. 13
    تركيزThe filtrate was concentrated in vacuo
14. 14
    أخرىPurification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent)

الإجراء التجريبي

To a stirred solution of 3-(3,5-dibromo-2-oxo-2H-pyrazin-1-yl)-4-methyl-benzoic acid, methyl ester (Example 1b, 0.1 g) in tetrahydrofuran (2 mL) was added triethylamine (0.17 mL) and 4-(2-aminoethyl)-phenol (34 mg). The reaction mixture was stirred for 12 h and 1-(2-chloroethyl)-pyrrolidine hydrochloride (120 mg), cesium carbonate (646 mg) and N,N-dimethylformamide (2 mL) were added. The mixture was heated within a microwave at 130° C. for 100 minutes. The reaction mixture was cooled to room temperature and quenched with sat. NaHCO3. The mixture was extracted with dichloromethane. The pooled organics were washed with water and brine, dried (Na2SO4), filtered and the solvent removed. The product was taken up in tetrahydrofuran (3 mL) followed by the addition of cyclopropylamine (0.15 mL) and cyclopentylmagnesium bromide (2M in diethyl ether, 0.75 mL) portionwise. The reaction mixture was stirred under nitrogen for 1 h before the addition of ethanol (2 mL), ammonium formate (300 mg) and 10% palladium on carbon (30 mg). The reaction mixture was heated within a microwave at 100° C. for 60 minutes, filtered and washed with ethanol. The filtrate was concentrated in vacuo. Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent) afforded the title compound (60 mg).

المصدر