Reaction Steps
To the product of Example 96F (150 mg, 0.31 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate [HATU] (132 mg, 0.21 mmol) in DMSO (1.5 mL) was added the product of Example 96H (49 mg, 0.32 mmol) and N,N-diisopropylethylamine (0.11 mL, 0.61 mmol) added dropwise at room temperature under N2. The mixture was stirred at room temperature for 2 hours, then poured into water (30 mL) with stirring. The resulting precipitate was extracted with ethyl acetate (1×30 mL). The organic layer was washed with water (3×15 mL) and 10% NaHCO3 (1×15 mL), dried over MgSO4, and concentrated. The residue was purified by column chromatography (SiO2, gradient elution of ethyl acetate/MeOH=98/2 to 95/5) to give a yellow solid. Trituration of product containing fractions with ethyl acetate gave the title compound as pale yellow crystal (86 mg, 48%). 1H-NMR (300 MHz, DMSO-d6) δ ppm: 1.34 (d, J=7.0 Hz, 6H), 1.69 (s, 3H), 3.23 (septet, J=7.0 Hz, 1H), 3.52 (dd, J=11.0, 6.3 Hz, 1H), 3.74 (dd, J=11.0, 5.9 Hz, 1H), 5.09 (dd, J=6.3, 5.9 Hz, 1H), 5.61 (s, 2H), 6.79 (dd, J=9.2, 8.4 Hz, 1H), 6.95 (d, J=8.5 Hz, 1H), 6.99 (dd, J=8.4, 1.8 Hz, 1H), 7.08 (dd, J=11.4, 1.8 Hz, 1H), 7.17 (br-t, J=7.0 Hz, 1H), 7.27 (t, J=7.0 Hz, 2H), 7.33 (br-d, J=7.0 Hz, 2H), 7.64 (d, J=8.4 Hz, 1H), 7.69 (dd, J=8.5, 1.8 Hz, 1H), 7.87 (d, J=1.8 Hz, 1H), 8.07 (s, 1H), 8.58 (s, 1H), 8.86 (d, J=8.4 Hz, 1H), 10.17 (s, 1H). MS ESI+ m/z: 583 (M+H), ESI− m/z: 581 (M−H).
