(2-Methoxyethyl)urea → 1-(3-(4-fluorophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(2-methoxyethyl)urea

Temperature

60 °C

6-Chloro-3-(4-fluorophenyl)-1H-pyrazolo[4,3-c]pyridine (433 mg, 1.748 mmol), 1-(2-methoxyethyl)urea (313 mg, 2.65 mmol) and chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-i-propyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (97 mg, 0.121 mmol) were taken up in THF (10.5 mL) in a 20 mL microwave vial. 1 M potassium t-butoxide in THF (5.25 mL, 5.25 mmol) was added and the vial was evacuated and back-filled with N2 (x3). The reaction mixture was stirred at 60° C. for 18 hours. Room temperature was attained and the mixture filtered through Celite, eluting with MeOH. The filtrate was concentrated in vacuo and the residue purified by MPLC (0-10% MeOH-EtOAc). The product was then triturated in EtOH to give 1-(3-(4-fluorophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(2-methoxyethyl)urea (237 mg, 0.720 mmol, 41.2% yield). MS ESI calc'd. for C16H17FN5O2 [M+H]+ 330, found 330. 1H NMR (600 MHz, DMSO-d6) δ 13.21 (s, 1H), 9.15 (s, 1H), 9.04 (s, 1H), 8.07-8.04 (m, 2H), 7.72 (s, 1H), 7.35-7.31 (m, 3H), 3.39 (t, J=5.5 Hz, 2H), 3.32-3.29 (m, 2H), 3.27 (s, 3H).

1. customthe vial was evacuated
2. additionback-filled with N2 (x3)
3. customRoom temperature
4. filtrationthe mixture filtered through Celite
5. washeluting with MeOH
6. concentrationThe filtrate was concentrated in vacuo
7. customthe residue purified by MPLC (0-10% MeOH-EtOAc)
8. customThe product was then triturated in EtOH

ORD record

ord-40cf110bfb3f4b6891eee6fabd402daf

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09023865B2