Trifluoroacetic acid → (1S,4R,5S,8S,14R)-8-((S)-3-Butyl-2-oxo-pyrrolidin-1-yl)-5-(3,5-difluoro-benzyl)-4-hydroxy-18-methoxy-13-oxa-2,6-diaza-tricyclo[12.6.1.015,20]henicosa-10,15(20),16,18-tetraen-7-one

Participants

Reaction Steps

Step J (2): Hoveyda-Grubb's catalyst [(1,3-bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(O-isoproproxylphenylmethylene)ruthenium] (6.6 mg, 7.8 μmol, Aldrich) was added to flask charge with a solution 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-((S)-3-butyl-2-oxopyrrolidin-1-yl)pent-4-enamide (59 mg, 0.0783 mmol, TFA salt) from stepH(1) in CH2Cl2 at room temperature. The mixture was stirred for 3 days. The resulting solution was evaporated to dryness, dissolved in MeOH, and filtered through Celite. Purified using reverse phase preparatory HPLC to give 26.2 mg (46% yield) of the title compound as a TFA salt: LC-MS (M+H)+=612.51; 1H NMR (500 MHz, CDCl3) δ 7.35 (d, J=8.55 Hz, 1H), 7.14 (s, 1H), 6.92-7.10 (m, 2H), 6.41-6.80 (m, 3H), 5.59-5.74 (m, 1H), 5.43-5.57 (m, 1H), 4.78-5.16 (m, 4H), 4.72 (d, J=5.49 Hz, 1H), 4.40 (d, J=9.77 Hz, 1H), 3.98-4.16 (m, 2H), 3.66-3.98 (m, 4H), 3.07-3.39 (m, 3H), 2.47-2.85 (m, 3H), 2.24-2.50 (m, 2H), 1.93-2.20 (m, 2H), 1.68-1.88 (m, 1H), 1.05-1.53 (m, 6H), 0.74-0.94 (m, 3H).

Provenance & Evidence