반응 #45110

반응 방정식

Trimethylaluminium

5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine

methyl 2-(3,4,6,7,8,8a-hexahydro-1H-pyrrolo[2,1-c]pyrazin-2-yl)pyrimidine-5-carboxylate

→

title compound

수율 30.0%

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

수율 30.0%

용매

toluene

반응 조건

후처리

1. 1
   workup.WAITat 60° C. for 2 h
2. 2
   기타The reaction mixture was quenched with methanol (20 mL)
3. 3
   workup.ADDITIONtreated with HCl (2N aqueous solution
4. 4
   기타until a freely stirred solution was obtained)
5. 5
   기타The crude product was purified by ion exchange chromatography
6. 6
   세척The desired product was eluted from the column
7. 7
   기타evaporated to dryness
8. 8
   기타to afford impure product
9. 9
   기타The impure material was purified by preparative HPLC
10. 10
    workup.ADDITIONFractions containing the desired compound
11. 11
    기타were evaporated to dryness

실험 절차

Trimethylaluminium (2M in toluene, 2.55 ml, 5.10 mmol) was added dropwise to a stirred suspension of 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (504 mg, 2.04 mmol) and methyl 2-(3,4,6,7,8,8a-hexahydro-1H-pyrrolo[2,1-c]pyrazin-2-yl)pyrimidine-5-carboxylate (535 mg, 2.04 mmol) in toluene (10.20 ml) at 25° C. The resulting solution was stirred at ambient temperature for 18 h and then at 60° C. for 2 h. The reaction mixture was quenched with methanol (20 mL) and treated with HCl (2N aqueous solution, until a freely stirred solution was obtained). The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and evaporated to dryness to afford impure product. The impure material was purified by preparative HPLC, using decreasingly polar mixtures of water (containing 0.1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the title compound (288 mg, 30%) as a solid.

출처