تفاعل #307759

معادلة التفاعل

3′-chloro-4-(1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl

4-(cyanomethyl)benzene boronic acid

potassium carbonate

water

water

→

title compound

المردود 58.0%

{4-[4-(1-Phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-phenyl}-acetonitrile hydrochloride

المردود 58.0%

المذيبات

N,N-dimethylacetamide

ظروف التفاعل

المعالجة

1. 1
   استخلاصextract with DCM (3×20 mL)
2. 2
   تركيزconcentrate
3. 3
   أخرىpurify
4. 4
   غسيل(silica gel chromatography, eluting with 5:95 to 15:85 methanol:DCM)
5. 5
   أخرىDry in a vacuum oven over night
6. 6
   أخرىfurther purify by low pH reverse phase HPLC
7. 7
   غسيلwashing with methanol
8. 8
   غسيلthen eluting with 2 M ammonia in methanol
9. 9
   تركيزconcentrate
10. 10
    workup.DISSOLUTIONDissolve the solid in acetonitrile
11. 11
    workup.ADDITIONby adding 2 M aq HCl solution

الإجراء التجريبي

Stir together 3′-chloro-4-(1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (177 mg, 0.50 mmol), 4-(cyanomethyl)benzene boronic acid (97 mg, 0.60 mmol), potassium carbonate (166 mg, 1.20 mmol) and tetrakis(triphenylphosphine) palladium(0) (0.006 g, 0.003 mmol) and water (1 mL), in N,N-dimethylacetamide (2 mL) at room temperature under nitrogen, then heat at 120° C. for 3 hr. Cool to room temperature, add water (20 mL) and extract with DCM (3×20 mL). Pass the combined DCM extracts through an IST Phase Separator Frit®, concentrate and purify (silica gel chromatography, eluting with 5:95 to 15:85 methanol:DCM). Dry in a vacuum oven over night, then further purify by low pH reverse phase HPLC. Form the free base by passing through an SCX-2® ion exchange cartridge washing with methanol then eluting with 2 M ammonia in methanol and concentrate. Dissolve the solid in acetonitrile and convert to the hydrochloride salt by adding 2 M aq HCl solution. Add water and lyophilize to give the title compound as a bright yellow solid (136 mg, 58%). MS (ES): m/z=436 [M+H]+.

المصدر