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

Temperature

60 °C

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.

1. stirringthe mixture was further stirred at 60° C. for 1 hr
2. temperatureThe reaction mixture was cooled to room temperature
3. washwashed successively with 5% aqueous ammonium chloride solution (10 ml), saturated aqueous sodium hydrogen carbonate solution (5 mL) and saturated brine (5 mL)
4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
5. concentrationconcentrated under reduced pressure
6. dissolutionThe obtained residue was dissolved in trifluoroacetic acid (4 mL)
7. stirringthe mixture was stirred at room temperature for 1 hr
8. concentrationThe reaction mixture was concentrated under reduced pressure
9. additionthe obtained residue was diluted with ethyl acetate (20 mL)
10. washwashed successively with saturated aqueous sodium hydrogen carbonate solution (20 mL) and saturated brine (20 mL)
11. dry with materialThe organic layer was dried over anhydrous sodium sulfate
12. concentrationconcentrated under reduced pressure
13. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→100/0)
14. customthe obtained oil residue was crystallized from ethyl acetate/heptane

ORD record

ord-cd427a87c0ff482ea92b7db8af78ec14

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697874B2