Trifluoroacetic acid → HCID 58529825, compound

To a cooled (0° C.) solution of tert-butyl 3-[(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)(hydroxy)methyl]azetidine-1-carboxylate (1.35 g, 4.25 mmol) in CH2Cl2 (12 mL) was added TFA (3.7 mL, 47.54 mmol) followed by triethylsilane (3.80 mL, 23.77 mmol), dropwise. The mixture was stirred at rt for 17 h. Additional TFA (1.8 mL) and triethylsilane (1.9 mL) were added and the mixture continued to stir at rt for 22 h. The reaction was concentrated to dryness. To a solution of the residue in THF (10 mL) was added 2M aqueous Na2CO3 (36 mL, 71.32 mmol) and di-tert-butyl carbonate (713 mg, 3.27 mmol). The mixture was stirred at rt for 17 h. The mixture was partitioned between EtOAc (50 mL) and H2O (25 mL) and the solid was removed by filtration. The layers of the filtrate were separated and the aqueous was further extracted with EtOAc (2×50 mL). The combined organics were washed with brine, dried (Na2SO4), and concentrated to dryness. The crude residue was purified by ISCO® chromatography using a gradient of 50 to 75% ethyl acetate in hexanes to afford 259 mg (29%) of the desired product. ES-MS m/z 304.02 [M+H]+, HPLC RT (min) 2.35.

1. stirringto stir at rt for 22 h
2. concentrationThe reaction was concentrated to dryness
3. stirringThe mixture was stirred at rt for 17 h
4. customThe mixture was partitioned between EtOAc (50 mL) and H2O (25 mL)
5. customthe solid was removed by filtration
6. customThe layers of the filtrate were separated
7. extractionthe aqueous was further extracted with EtOAc (2×50 mL)
8. washThe combined organics were washed with brine
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated to dryness
11. customThe crude residue was purified by ISCO® chromatography

ORD record

ord-d69adf9dfd404b2891c43cef64e4351e

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08431695B2