반응 #45104

반응 방정식

5-Chloro-N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]pyrazine-2-carboxamide

1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine

→

title compound

수율 37.4%

5-(3,4,6,7,8,8a-Hexahydro-1H-pyrrolo[2,1-c]pyrazin-2-yl)-N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]pyrazine-2-carboxamide

수율 37.4%

용매

dimethylsulfoxide

반응 조건

후처리

1. 1
   기타The residue was purified by ion exchange chromatography
2. 2
   세척The desired product was eluted from the column
3. 3
   기타to afford impure material
4. 4
   기타The concentrated eluent was purified by preparative HPLC
5. 5
   workup.ADDITIONFractions containing the desired compound
6. 6
   기타were evaporated to dryness
7. 7
   기타to afford impure product as a yellow solid
8. 8
   기타The impure material was then repurified by silica column chromatography
9. 9
   세척eluting with a gradient of 0 to 5% 7M NH3/MeOH in DCM
10. 10
    기타Pure fractions were evaporated to dryness

실험 절차

5-Chloro-N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]pyrazine-2-carboxamide (585 mg, 1.50 mmol) was added in one portion to 1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine (379 mg, 3.00 mmol) in anhydrous dimethylsulfoxide (1.50 ml) at 25° C. The resulting solution was stirred at 100° C. for 18 h. The residue was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH to afford impure material. The concentrated eluent was purified by preparative HPLC, using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford impure product as a yellow solid. The impure material was then repurified by silica column chromatography, eluting with a gradient of 0 to 5% 7M NH3/MeOH in DCM. Pure fractions were evaporated to dryness to afford the title compound (269 mg, 37%) as a yellow solid.

출처