Triethylsilane → 1-(4-(1-hydroxyethyl)-3-methoxy-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-((R)-1-phenylethyl)urea

Temperature

-78 °C

(R)-1-(4-Formyl-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (114 mg, 0.196 mmol) was dissolved in THF (3 mL), cooled to −78° C., and charged with methylmagnesium bromide (0.196 mL, 0.588 mmol). The reaction was allowed to warm to 0° C. and stirred for 10 min. The reaction mixture was quenched with saturated ammonium chloride (3 mL), extracted with EtOAc (10 mL, ×2), washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was dissolved in TFA (0.8 mL), charged with triethylsilane (0.031 mL, 0.196 mmol), and stirred at room temperature for 10 min. The reaction mixture was concentrated in vacuo and the residue was dissolved in DCM (2 mL) and TEA (1 mL) to free-base the product. The solvents were removed in vacuo and the residue was purified by flash chromatography (10-100% EtOAc/DCM) to give 1-(4-(1-hydroxyethyl)-3-methoxy-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-((R)-1-phenylethyl)urea. MS ESI calc'd. For C18H21N5O3 [M+1]+ 356. found 356.

1. temperatureto warm to 0° C.
2. customThe reaction mixture was quenched with saturated ammonium chloride (3 mL)
3. extractionextracted with EtOAc (10 mL, ×2)
4. washwashed with brine
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. dissolutionThe residue was dissolved in TFA (0.8 mL)
9. stirringstirred at room temperature for 10 min
10. concentrationThe reaction mixture was concentrated in vacuo
11. dissolutionthe residue was dissolved in DCM (2 mL)
12. customThe solvents were removed in vacuo
13. customthe residue was purified by flash chromatography (10-100% EtOAc/DCM)

ORD record

ord-42168c13309a49c68cc01414fb55a85d

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09226922B2