2-(((Tert-butoxy)carbonyl)amino)-2-phenylacetic acid → HCID 86657973, compound

Participants

Reaction Conditions

Reaction Steps

N-[5-(3-Amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide (200 mg, 0.58 mmol) produced in Example 16(vi) was dissolved in pyridine (3.0 mL), [(tert-butoxycarbonyl)amino](phenyl)acetic acid (290 mg, 1.2 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (440 mg, 1.2 mmol) were added, and the mixture was stirred at 60° C. for 7 hr. [(tert-Butoxycarbonyl)amino](phenyl)acetic acid (145 mg, 0.58 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (220 mg, 0.58 mmol) were added to the reaction mixture, and the mixture was further stirred at 60° C. for 1 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (10 mL), and washed successively with 5% aqueous ammonium chloride solution (10 ml), saturated aqueous sodium hydrogen carbonate solution (5 mL) and saturated brine (5 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was dissolved in trifluoroacetic acid (4 mL), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, and the obtained residue was diluted with ethyl acetate (20 mL), and washed successively with saturated aqueous sodium hydrogen carbonate solution (20 mL) and saturated brine (20 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→100/0), and the obtained oil residue was crystallized from ethyl acetate/heptane to give the title compound (150 mg, 53%) as a pale-yellow powder.

Provenance & Evidence