反应详情

Step I (2): The TFA salt of (S)—N-((2S,3R)-4-((1S,3R)-3-(Allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)-2-(2-oxopyrrolidin-1-yl)pent-4-enamide (diastereomer A, 10 mg, 0.0143 mmol) from stepG(1) was dissolved in 2 mL of CH2CL2. Added Hoveyda/Grubbs catalyst [(1,3-bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(O-isoproproxylphenylmethylene)ruthenium] (2.4 mg, 2.9 μmol, Aldrich) and stirred at room temperature overnight. Evaporated to dryness. Dissolved in MeOH and filtered. The crude product was purified using reverse phase preparatory HPLC to give 5.5 mg (70% yield) of the title compound as its TFA salt: LC-MS (M+H)+=556.31; HRMS (M+H)+=556.2603; 1H NMR (500 MHz, CDCl3) δ 7.27-7.43 (m, 1H), 7.04-7.21 (m, 1H), 6.99 (d, J=8.24 Hz, 1H), 6.40-6.83 (m, 3H), 5.42-5.79 (m, 2H), 4.98 (d, J=5.49 Hz, 1H), 4.71 (d, J=5.49 Hz, 1H), 4.25-4.51 (m, 1H), 4.06 (d, J=8.24 Hz, 1H), 3.87-4.06 (m, 2H), 3.72-3.91 (m, 3H), 3.36-3.72 (m, 3H), 3.16-3.39 (m, 2H), 3.06-3.21 (m, 1H), 2.92-3.08 (m, 1H), 2.76-2.89 (m, 1H), 2.54-2.76 (m, 2H), 2.17-2.54 (m, 3H), 1.86 (dd, J=14.34, 7.32 Hz, 2H), 0.91-1.52 (m, 2H).

1. customEvaporated to dryness
2. dissolutionDissolved in MeOH
3. filtrationfiltered
4. customThe crude product was purified