反应详情

温度

50 °C

To a solution of (R)-2-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yloxy]-propionic acid ethyl ester (315 mg, 0.77 mmol) in methanol (10 mL) was added water (1 mL) and lithium hydroxide monohydrate (46 mg, 1.15 mmol). The reaction mixture was heated at 50° C. for 16 h then HCl (1N, aq.) added until pH˜4. The reaction mixture was concentrated in vacuo. The resultant residue was dissolved in DMF (5 mL) and HATU (583 mg, 1.53 mmol), ammonium chloride (122 mg, 2.29 mmol) and triethylamine (320 μL, 2.29 mmol) added. The reaction mixture was stirred at RT for 1 h before being concentrated in vacuo. The residue was dissolved in ethyl acetate (10 mL) and the mixture washed with water, extracting with ethyl acetate (3×10 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-10% methanol in ethyl acetate) and the product crystallised from acetonitrile to give 485 as a white solid (75 mg, 26%). LCMS: RT=3.25 min, [M+H]+=383

1. concentrationThe reaction mixture was concentrated in vacuo
2. dissolutionThe resultant residue was dissolved in DMF (5 mL)
3. concentrationbefore being concentrated in vacuo
4. dissolutionThe residue was dissolved in ethyl acetate (10 mL)
5. washthe mixture washed with water
6. extractionextracting with ethyl acetate (3×10 mL)
7. washThe combined organic extracts were washed with brine
8. dry with materialdried (MgSO4)
9. concentrationconcentrated in vacuo
10. customthe product crystallised from acetonitrile