تفاعل #640691

معادلة التفاعل

potassium carbonate

4-cyanomethylphenyl boronic acid

1-methyl-1H-pyrazole-4-sulfonic acid [2-(3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-yl)-ethyl]-methyl-amide

DME

→

title compound

المردود 71.0%

1-Methyl-1H-pyrazole-4-sulfonic acid {2-[3′-(4-cyanomethyl-phenyl)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-yl]-ethyl}-methyl-amide hydrochloride

المردود 71.0%

المذيبات

ethyl acetate

water

DMA H2O

H2O

ظروف التفاعل

المعالجة

1. 1
   أخرى3:1 v/v, previously degassed with nitrogen)
2. 2
   درجة الحرارةCool
3. 3
   استخلاصExtract the aqueous layer with ethyl acetate
4. 4
   تجفيفDry the combined organic layers over sodium sulfate
5. 5
   ترشيحfilter
6. 6
   تركيزconcentrate
7. 7
   أخرىPurify by SCX chromatography
8. 8
   غسيلeluting with dichloromethane, dichloromethane:methanol 1:1, methanol, and 1N ammonia in methanol
9. 9
   أخرىPurify by silica gel chromatography
10. 10
    غسيلeluting with hexanes:acetone 1:1

الإجراء التجريبي

Dissolve 1-methyl-1H-pyrazole-4-sulfonic acid [2-(3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-yl)-ethyl]-methyl-amide (0.250 g, 0.625 mmol) in DMA-H2O (or DME:H2O) (6 mL; 3:1 v/v, previously degassed with nitrogen). Add 4-cyanomethylphenyl boronic acid (0.121 g, 0.750 mmol), potassium carbonate (0.207 g, 1.500 mmol) and tetrakis(triphenylphosphine)palladium (0.036 g, 0.031 mmol). Stir the reaction mixture at 110° C. for 18 hr. Cool and dilute with ethyl acetate and water. Extract the aqueous layer with ethyl acetate and combine the organic layers. Dry the combined organic layers over sodium sulfate, filter, and concentrate. Purify by SCX chromatography, eluting with dichloromethane, dichloromethane:methanol 1:1, methanol, and 1N ammonia in methanol. Purify by silica gel chromatography eluting with hexanes:acetone 1:1 to afford the free base of the title compound (0.214 g, 71% yield).

المصدر