Sodium Bicarbonate → HCID 56932880, compound

Participants

Reaction Conditions

Reaction Steps

A 250-mL round-bottomed flask was charged with 4-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3,3-dimethyl-2-piperazinone (0.314 g, 0.475 mmol, step 2), iron filings (0.136 g, 2.43 mmol) and AcOH (10 mL). The reaction mixture was heated at 50° C. for 3 h. An additional 0.052 g of iron filing was added and the heating at 50° C. was continued for 30 min. The mixture was allowed to cool to room temperature and then saturated aqueous NaHCO3 (300 mL) was slowly added. The aqueous phase was extracted with EtOAc (3×100 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by preparative HPLC (Phenomenex 5 μm, C18 column, 150×30 mm) eluting with 10 to 90% ACN with 0.1% TFA in H2O with 0.1% TFA in 15 min. The fractions were concentrated and basified with saturated aqueous NaHCO3. The resulting solid was collected (0.130 g). The aqueous phase was extracted with 10% iPrOH in CHCl3 containing 1% NH4OH. The combined organic extracts were dried over sodium sulfate, filtered and concentrated to obtain an additional 0.265 g. The combined material was purified by column chromatography (25 g of silica gel, 0 to 10% (2M NH3 in MeOH) in CH2Cl2 to afford 4-(((2S)-4-((5-amino-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3,3-dimethyl-2-piperazinone (0.084 g) as an off-white solid.

Provenance & Evidence