تفاعل #1277474
ord-e86246616aae4c7c8905c7fa95645193
معادلة التفاعل
المتفاعلات
الكواشف
المذيبات
ظروف التفاعل
المعالجة
- 1workup.ADDITIONwas added
- 2استخلاصthe mixture extracted with 1:1 EtOAc/THF solution (×2)
- 3غسيلwashed with brine
- 4تجفيفdried (Na2SO4)
- 5تركيزconcentrated in vacuo
- 6workup.ADDITIONThe resulting solid was added to DMF (50 mL)
- 7درجة الحرارةto cool to RT
- 8استخلاصextracted with EtOAc
- 9غسيلwashed with water
- 10تجفيفThe organic layer was dried (Na2SO4)
- 11تركيزconcentrated in vacuo
- 12أخرىThe resultant residue was purified by flash chromatography (SiO2, gradient 0-50% EtOAc in cyclohexane)
الإجراء التجريبي
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