Ammonia → (S)-tert-Butyl (1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)carbamate

Triphenylphosphine (6.8 g, 25.93 mmol) was dissolved in 50 mL dichloromethane. Bromine (1.33 mL, 25.97 mmol) was added dropwise and the reaction was stirred at room temperature for 30 min. Triethylamine (10.3 mL, 73.9 mmol) and (S)-tert-butyl (1-((3-methyl-2-(phenylcarbamoyl)-1H-pyrrol-1-yl)amino)-1-oxopropan-2-yl)carbamate (7.15 g, 18.5 mmol) suspended in 100 mL dichloromethane was added and the reaction mixture was stirred at 60° C. for 2 h. The mixture was concentrated to dryness and was re-dissolved in a pressure reactor with a solution of ammonia (7M in methanol, 350 mL, 2415 mmol). The mixture was heated at 100° C. for 32 h, then cooled at room temperature and evaporated under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic layer was washed with water, brine and dried over sodium sulphate, filtered and concentrated. The residue was purified using Isolera® Purification System (0% to 50%, hexane-ethyl acetate) to obtain 0.95 g (14% yield) of the title compound as a yellow solid.

1. additionwas added
2. stirringthe reaction mixture was stirred at 60° C. for 2 h
3. concentrationThe mixture was concentrated to dryness
4. temperatureThe mixture was heated at 100° C. for 32 h
5. temperaturecooled at room temperature
6. customevaporated under reduced pressure
7. customThe residue was partitioned between ethyl acetate and water
8. washThe organic layer was washed with water, brine
9. dry with materialdried over sodium sulphate
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was purified
13. customIsolera® Purification System (0% to 50%, hexane-ethyl acetate)

ORD record

ord-05770dab476f4b88a773667ed327ef02

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09388189B2