反应详情

To a suspension of NaH (19.5 mg of 60% dispersion in mineral oil, 0.488 mmol) in DMF (2 mL), methyl 2-(4-(tert-butoxycarbonyl)pyridin-3-yl)-3-cyclohexyl-1H-indole-6-carboxylate (100 mg, 0.222 mmol) was added and the reaction mixture was stirred at rt for 10 min. Allyl bromide (0.040 mL, 0.466 mmol) was then added, and the reaction mixture was stirred at rt for 3 hr. It was then quenched by the addition of water and acidified using 1N HCl solution. A yellowish precipitate formed which was collected by filtration to give the crude ester product in sufficient purity to proceed to the next step. This material was then dissolved in a THF/Methanol mixture (3 mL/3 mL) and 2N NaOH solution (2 mL) was added. The reaction mixture was heated at 100° C. under microwave conditions for 15 min. It was then concentrated and the pH was adjusted to 4–5 using 1N HCl solution. This mixture was then extracted using ethyl acetate and the organic layer was dried with MgSO4, filtered and evaporated and the resultant residue was purified using Prep. reverse phase HPLC to afford the title compound as a yellow solid, (50 mg, 44% yield two steps). MS m/z 516(MH+); 1H NMR (500 MHz, CD3OD) □ ppm 1.22–1.48 (m, 13 H) 1.70–2.02 (m, 5 H) 2.15 (m, 1 H) 2.37 (m, 1 H) 3.88 (dd, J=16.63, 5.04 Hz, 1 H) 4.13 (m, 1 H) 4.51 (m, 1 H) 4.76 (m, 1 H) 4.87 (m, 1 H) 5.04–5.21 (m, 3 H) 5.79 (m, 1 H) 5.97 (m, 1 H) 7.58 (d, J=5.80 Hz, 1 H) 7.78 (m, 1 H) 7.90 (d, J=8.24 Hz, 1 H) 8.13 (s, 1 H) 8.50 (s, 1 H) 8.67 (d, J=5.80 Hz, 1 H).

1. additionwas added
2. stirringthe reaction mixture was stirred at rt for 3 hr
3. customIt was then quenched by the addition of water
4. customA yellowish precipitate formed which
5. filtrationwas collected by filtration
6. customto give the crude ester product in sufficient purity
7. additionwas added
8. temperatureThe reaction mixture was heated at 100° C. under microwave conditions for 15 min
9. concentrationIt was then concentrated
10. extractionThis mixture was then extracted
11. dry with materialthe organic layer was dried with MgSO4
12. filtrationfiltered
13. customevaporated
14. customthe resultant residue was purified