Tetrahydrofuran → [1(S)-Benzyl-2-(2(R)-{4-[3-(5-chloro-2-hydroxy-phenyl)-1-(2-hydroxy-ethyl)-1H-pyrazol-4-ylethynyl]-phenylcarbamoyl}-piperidin-1-yl)-2-oxo-ethyl]-methyl-carbamic acid tert-butyl ester

Participants

Reaction Steps

To a mixture of compound 5A (6.50 g, 13.98 mmol) and BOC-N-Me-Phe-OH (6A, 9.76 g, 34.94 mmol) was added anhydrous THF (350 mL) and the resultant mixture was stirred at rt for 10 min. Diisopropylcarbodiimide (DIPC, 5.41 mL, 34.94 mmol) was added slowly at rt. The reaction mixture was stirred at rt overnight. Water (˜10 mL) was added to the above mixture and the reaction mixture was stirred at rt for 3 hour. Solvent was removed and the residua were dissolved in ethyl acetate. It was filtered to remove solid (diisopropylurea). The filtrate was purified by silica column chromatography eluting with hexanes-ethyl acetate (v/v 1/1, 2/3, 1/2) to provide the title compound (7A, 4.3 g) as foam-like powder in 42.3% yield. 1H NMR (CDCl3, 500 MHz) δ 10.63 (s, 1H), 8.67 (s, 1H), 8.62 (s, 1H), 7.76 (s, 1H), 7.63 (m, 1H), 7.52 (d, 2H, J=7.5 Hz), 7.40-7.10 (m, 7H), 6.96 (d, 1H, J=8.0 Hz), 5.35 (br s, 1H), 5.13 (m, 1H), 4.29 (s, 2H), 4.05 (s, 2H), 3.81 (m, 1H), 3.20 (t, 1H, J=8.0 Hz), 3.09 (m, 2H), 2.94 (s, 3H), 2.87 (m, 1H), 2.35 (m, 1H), 1.75-1.10 (m, 12H), 0.74 (m, 1H). LCMS (ESI) m/z 748.26 (MNa+), 726.27 (MH+), 670.21, 626.20, 465.10, 373.18, 317.14 (100). HPLC: tR=5.70 min.

Provenance & Evidence