Methyl iodide → 1-[2-fluoro-4-(3-methyl-2-oxoimidazolidin-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

HRID 1805721Notes

Reaction equation

HRID 1805721 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:12][CH2:11][NH:10][C:9]2=[O:13])[CH:5]=[CH:4][C:3]=1[N:14]1[CH:19]=[C:18]([O:20][CH3:21])[C:17](=[O:22])[C:16]([C:23]2[N:27]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[N:26]=[CH:25][CH:24]=2)=[N:15]1.I[CH3:35].[H-].[Na+]>CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:12][CH2:11][N:10]([CH3:35])[C:9]2=[O:13])[CH:5]=[CH:4][C:3]=1[N:14]1[CH:19]=[C:18]([O:20][CH3:21])[C:17](=[O:22])[C:16]([C:23]2[N:27]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[N:26]=[CH:25][CH:24]=2)=[N:15]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 580724131-[2-Fluoro-4-(2-oxoimidazolidin-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Product 1

HCID 580724391-[2-fluoro-4-(3-methyl-2-oxoimidazolidin-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-oneYield 59%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 1-[2-fluoro-4-(2-oxoimidazolidin-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (40 mg, 0.09 mmol), iodomethane (0.02 mL, 0.36 mmol), and sodium hydride (60% in oil) (7.0 mg, 0.18 mmol) in DMF (4.0 mL) was stirred at 0° C. for 2 h. The reaction mixture was quenched with H2O, and extracted with AcOEt. The organic layer was dried over MgSO4, and concentrated under reduced pressure. The residue was recrystallized from iPr2O/AcOEt to give the title compound (24 mg, 59% yield) as a white solid: mp 208-209° C.; 1H NMR (300 MHz, DMSO-d6): δ ppm 2.79 (3H, s), 3.42-3.58 (2H, m), 3.77 (3H, s), 3.78-3.86 (2H, m), 6.95 (1H, d, J=1.9 Hz), 7.01 (1H, t, J=9.0 Hz), 7.22-7.51 (6H, m), 7.73 (1H, dd, J=14.1, 2.4 Hz), 7.78 (1H, d, J=1.9 Hz), 8.44 (1H, d, J=1.9 Hz). LC-MS (ESI) m/z 461 [M+H]+. Anal. Calcd for C24H21FN6O3.0.75H2O: C, 60.06; H, 4.49; N, 18.27. Found: C, 60.05; H, 4.26; N, 18.16.

Workup

  1. customThe reaction mixture was quenched with H2O
  2. extractionextracted with AcOEt
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was recrystallized from iPr2O/AcOEt

Sources & evidence

ORD record
ord-b4dd1c234fb449ed99997b3897990a2f
Source dataset
uspto-grants-2013_01
Patent number
US08354411B2

Reaction notes

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