1-Hydroxybenzotriazole → (2beta,3alpha,5alpha)-3-hydroxy-2-(4-{[(2S)-1-(isoquinolin-3-ylcarbonyl)pyrrolidin-2-yl]carbonyl}piperazin-1-yl)androstan-17-one

Participants

Reaction Steps

To a solution of compound 23 (356 mg, 0.95 mmol) in anhydrous DMF (5 mL) at room temperature under an atmosphere of argon were added 1-(isoquinolin-3-ylcarbonyl)-L-proline (335 mg, 1.2 mmol), PyBOP (647 mg, 1.2 mmol), HOBt (168 mg, 1.2 mmol), and DIPEA (662 μL, 3.8 mmol). The solution was subsequently stirred overnight at room temperature. The resulting solution was then poured into water and extracted with EtOAc (2×30 mL), washed with brine, dried with MgSO4 and evaporated to dryness. Purification by two successive flash chromatography procedures using (DCM/MeOH: 95:5) and (Hexanes/Acetone: 1:1) respectively yielded 302 mg (50%) of compound 43. 1H NMR (CDCl3) δ: 0.84 and 0.86 (2s, 18-CH3), 0.89 and 0.90 (2s, 19-CH3), 0.70-2.30 (residual CH and CH2), 2.35-2.85 (broad m, 2×CH2N, 16β-CH and 2α-CH), 3.10-4.27 (broad m, 2×CH2NCO, CH2N of proline, and 3β-CH), 5.10 and 5.88 (2m, NCHCO of proline), 7.58 (m, CH of quinoline), 7.76 (m, CH of quinoline), 7.84 (t, J=8.3 Hz, CH of quinoline), 7.98 (t, J=8.7 Hz, CH of quinoline), 8.02 and 8.12 (2d, J=8.6 Hz, CH of quinoline), 8.21 and 8.24 (2d, J=8.9 Hz, CH of quinoline).

Provenance & Evidence