Water → 5-Cyano-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [1-(S)-(4-fluorobenzyl)-2-(4-hydroxypiperidin-1-yl)-2-oxoethyl]amide

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Reaction Steps

To a solution of 2-(S)-amino-3-(4-fluorophenyl)-1-(4-hydroxypiperidin-1-yl)propan-1-one hydrochloride (Preparation 20, 0.036 g, 0.118 mmol) in DMF (anhydrous, 5 mL) was added DIPEA (0.061 mL, 0.353 mmol) then carboxylic acid (Preparation 62, 0.020 g, 0.107 mmol). To the stirred solution was added HOBt.H2O (0.016 g, 0.107 mmol) then, after 10 min, EDCI (0.025 g, 0.128 mmol). The reaction mixture was stirred for 18 h then all volatiles were removed in vacuo. The residue was partitioned between CH2Cl2 (30 mL) and water (20 mL). The layers were separated then the aqueous was extracted with CH2Cl2 (2×30 mL). The combined organics were washed with brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was dissolved in methanol then adsorbed onto silica gel. Purification via flash column chromatography (SiO2, methanol:dichloromethane, 7:93, v/v) gave the title compound as a white solid. δH (d6 DMSO): 1.05–1.32 (2H, m), 1.49–1.72 (2H, m), 2.86–3.42 (4H, m), 3.53–3.87 (2.5H, m), 3.93–4.05 (0.5H, m), 4.69 (1H, d), 5.07–5.21 (1H, m), 6.97–7.12 (2H, m), 7.26–7.39 (2H, m), 7.47 (1H, s), 8.41 (1H, s), 8.81 (1H, s), 9.01–9.41 (1H, m), 12.64 (1H, s); m/z (ES+)=436 [M+H]+; RT=1.51 min.

Provenance & Evidence