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

HRID 571428Notes

Reaction equation

HRID 571428 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)=[N:9][NH:10][C:4]=2[CH:3]=1.[CH3:18][O:19][CH2:20][CH2:21][NH:22][C:23]([NH2:25])=[O:24].CC(C)([O-])C.[K+]>C1COCC1.CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+]>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:8]2[C:5]3[CH:6]=[N:7][C:2]([NH:25][C:23]([NH:22][CH2:21][CH2:20][O:19][CH3:18])=[O:24])=[CH:3][C:4]=3[NH:10][N:9]=2)=[CH:12][CH:13]=1

Participants

6

Reactant 3

HCID 186068(2-Methoxyethyl)ureaHCID 23665647Potassium tert-butoxideHCID 768471656-Chloro-3-(4-fluorophenyl)-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 895258561-(3-(4-fluorophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(2-methoxyethyl)ureaYield 41.2%

Reagents, catalysts & solvents 2

HCID 25112666BrettPhos PalladacycleCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-40cf110bfb3f4b6891eee6fabd402daf
Source dataset
uspto-grants-2015_05
Patent number
US09023865B2

Reaction notes

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