Potassium Fluoride → HCID 86679987, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-chloro-1-(4-methoxybenzyl)-4-nitro-1H-pyrazole (268 mg, 1.0 mmol) and potassium fluoride (232 mg, 4.0 mmol) in dry DMSO (20 mL) was added (S)-tert-butyl 3-methylpiperazine-1-carboxylate (230 mg, 1.15 mmol) and the mixture heated in the microwave at 100° C. for 8 hr. The mixture was partitioned between water (30 mL) and EtOAc (50 mL) and the organic layer was passed through a phase separation cartridge and concentrated under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave (S)-tert-butyl 4-(1-(4-methoxybenzyl)-4-nitro-1H-pyrazol-5-yl)-3-methylpiperazine-1-carboxylate as a yellow gum (380 mg). To a solution of this gum (371 mg, 0.86 mmol) in ethanol/water (20 mL/2 mL) was added ammonium chloride (230 mg, 4.3 mmol) and iron powder (192 mg, 3.44 mmol.) and the mixture heated at 80° C. for 1.5 hr. The mixture was cooled, filtered through Celite® and concentrated under reduced pressure. The residue was partitioned between water (30 mL) and DCM (40 mL) and the organic layer was separated, passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification via silica gel column chromatography (0-5% MeOH/DCM) gave (S)-tert-butyl 4-(4-amino-1-(4-methoxybenzyl)-1H-pyrazol-5-yl)-3-methylpiperazine-1-carboxylate as a red gum (330 mg, 84% over two steps). 1H NMR (400 MHz, CDCl3) δ 7.17-7.11 (m, 3H), 6.82 (d, J=8.6 Hz, 2H), 5.34 (d, J=14.4 Hz, 1H), 5.17 (d, J=14.4 Hz, 1H), 3.98-3.80 (m, 2H), 3.78 (s, 3H), 3.23 (ddd, J=9.9, 6.4, 3.3 Hz, 1H), 3.01 (td, J=11.4, 3.0 Hz, 1H), 2.92-2.83 (m, 1H), 2.66 (s, 1H), 2.57 (s, 1H), 1.47 (s, 9H), 0.81 (d, J=6.3 Hz, 3H).

Provenance & Evidence