Sodium borohydride → HCID 69448198, compound

Participants

Reaction Steps

A solution of the product of Step 1 (90 mg, 0.25 mmol), in EtOH (10 mL) was treated with NaBH4 (38 mg, 1.0 mmol) and stirred at RT for 1 h. The reaction was quenched with NH4Cl solution, then the EtOH was removed under reduced pressure. The residue was partitioned between CH2Cl2 and water and the organic layer separated and the aqueous re-extracted with CH2Cl2. The combined organic extracts were dried (MgSO4) and concentrated under reduced pressure to give 1-(4-chloro-phenyl)-3-[4-(2-ethyl-5-methyl-2H-pyrazol-3-yl)-piperidin-1-yl]-propan-1-ol as a gum (30 mg). This intermediate was dissolved in THF (5 mL), treated with N-methylbenzenesulfonamide (17 mg, 0.1 mmol), PPh3 (26 mg, 0.1 mmol) and DIAD (20 μL, 0.1 mmol) and stirred overnight at RT. The solvent was evaporated under reduced pressure and the residue dissolved in CH2Cl2 and loaded onto a 5 g SCX cartridge, which was eluted with CH2Cl2 then 2M NH3 in MeOH solution. The fractions containing the desired material were concentrated under reduced pressure and were further purified by silica chromatography eluting 1–3% MeOH/CH2Cl2 to yield the desired sulfonamide. 1H NMR (CDCl3, 400 MHz) δ 7.70 (2H, d, J=7.3 Hz), 7.48 (1H, d, J=7.3 Hz), 7.40 (2H, t, J=7.3 Hz), 7.20–7.15 (2H, m), 7.07 (2H, d, J=8.4 Hz), 5.73 (1H, s), 5.07 (1H, t, J=7.3 Hz), 3.94 (2H, q, J=7.4 Hz), 2.92–2.68 (2H, m), 2.60 (3H, s), 2.48–2.32 (1H, m), 2.28–2.05 (5H, m), 2.05–1.40 (8H, m), 1.33 (3H, t, J=7.4 Hz). MS (ES+) C27H35ClN4O2S requires: 515, found: 515/517 (3:1, M+H+)

Provenance & Evidence