Potassium Fluoride → HCID 86679971, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-chloro-1-methyl-4-nitro-1H-pyrazole from Example 1 (355 mg, 2.2 mmol) and potassium fluoride (511 mg, 8.8 mmol) in dry DMSO (20 mL) was added (R)-tert-butyl 3-methylpiperazine-1-carboxylate (507 mg, 2.53 mmol) and the mixture was heated in the microwave at 100° C. for 10 hr. The mixture was partitioned between water (40 mL) and EtOAc (100 mL) and the organic layer passed through a phase separation cartridge and concentrated under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave (R)-tert-butyl 3-methyl-4-(1-methyl-4-nitro-1H-pyrazol-5-yl)piperazine-1-carboxylate as an orange gum (627 mg). To a solution of this gum (179 mg, 0.55 mmol) and ammonium formate (256 mg, 4.4 mmol) in MeOH (10 mL) under nitrogen was added 10% palladium on carbon (59 mg, 0.55 mmol). The mixture was heated at 70° C. for 4 hr before being cooled, filtered and concentrated under reduced pressure. The residue was partitioned between water (20 mL) and DCM (60 mL) and the organic layer separated, passed through a phase separation cartridge and concentrated under reduced pressure to give (R)-tert-butyl 4-(4-amino-1-methyl-1H-pyrazol-5-yl)-3-methylpiperazine-1-carboxylate as a brown gum (150 mg, 80% over two steps). LCMS (ES+) m/z 296 (M+1).

Provenance & Evidence