반응 #46108

반응 방정식

diethyl malonate

5-Methyl-2H-pyrazol-3-ylamine

NaOEt

→

2-methyl-4H-pyrazolo[1,5-a]pyrimidine-5,7-dione

용매

EtOH

반응 조건

후처리

1. 1
   기타(prepared in an analogous procedure to
2. 2
   온도The mixture was heated
3. 3
   온도at reflux for 3 h
4. 4
   여과the precipitate was collected by filtration
5. 5
   세척washed with additional EtOH
6. 6
   기타dried

실험 절차

(prepared in an analogous procedure to that outlined in WO 2004/026229 A2) Step A: 5-Methyl-2H-pyrazol-3-ylamine (2 g, 0.0206 mol) was dissolved in EtOH (60 ml) and NaOEt (11.58 ml of a 21% by wt. solution, 2 eq) was added, followed by diethyl malonate (3.44 ml, 1.1 eq). The mixture was heated at reflux for 3 h. After cooling to rt, the precipitate was collected by filtration, washed with additional EtOH, and dried to give 1.6 g of 2-methyl-4H-pyrazolo[1,5-a]pyrimidine-5,7-dione. Step B: The compound from step A (1.6 g) was dissolved in POCl3 (18 ml) and cooled to 0° C., N,N-dimethylaniline (3.43 ml) was added and the mixture heated at 115-120° C. overnight. After cooling to rt, the POCl3 was removed under reduced pressure, the resulting residue was taken up in CH2Cl2, and poured onto ice. Once the ice melted the mixture was neutralized with NaHCO3 (s) and the organic layer separated. The organic layer was washed with water, dried (MgSO4), concentrated under reduced pressure, and the resulting residue purified by flash chromatography (SiO2, hexane-CH2Cl2) to give 0.734 g of 5,7-dichloro-2-methylpyrazolo[1,5-a]pyrimidine. 1H NMR (CDCl3) δ 6.89 (s, 1H), 6.52 (s, 1H), 2.55 (s, 3H).

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