반응 #795015
ord-6e0357c0239247ff868129bd225bbaa9
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후처리
- 1workup.ADDITIONwas added
- 2추출the mixture extracted with 1:1 EtOAc/THF solution (×2)
- 3세척washed with brine
- 4건조dried (Na2SO4)
- 5농축concentrated in vacuo
- 6workup.ADDITIONThe resulting solid was added to DMF (50 mL)
- 7온도to cool to RT
- 8추출extracted with EtOAc
- 9세척washed with water
- 10건조The organic layer was dried (Na2SO4)
- 11농축concentrated in vacuo
- 12기타The resultant residue was purified by flash chromatography (SiO2, gradient 0-50% EtOAc in cyclohexane)
실험 절차
To a suspension of 8-bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (1.86 g, 5.70 mmol) in anhydrous THF (75 mL) was added diisopropylethylamine (2 mL, 11.4 mmol), HATU (2.39 g, 6.27 mmol) and 1-benzyloxycarbonyl-2-methyl-isothiourea (1.47 g, 6.56 mmol) at RT. After stirring for 24 hours an aqueous saturated sodium bicarbonate solution was added and the mixture extracted with 1:1 EtOAc/THF solution (×2). The organic layers were combined, washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting solid was added to DMF (50 mL) and treated with diisopropylethylamine (4 mL, 22.8 mmol) and isopropylhydrazine hydrochloride (941 mg, 8.55 mmol). The mixture was heated to 95° C. and scrubbed with 1N NaOH solution and NaOCl solution. After 2 hours the mixture was allowed to cool to RT, extracted with EtOAc and washed with water. The organic layer was dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography (SiO2, gradient 0-50% EtOAc in cyclohexane) to afford [5-(8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl)-1-isopropyl-1H-[1,2,4]triazol-3-yl]-carbamic acid benzyl ester (1.75 g, 57%). LCMS: RT=5.11 min, [M+H]+=540/542