N,N'-Dimethylethylenediamine → 1-[2-Fluoro-3-(2-oxopiperidin-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

HRID 1895376Notes

Reaction equation

HRID 1895376 reaction equation
Br[C:2]1[C:3]([F:28])=[C:4]([N:8]2[CH:13]=[C:12]([O:14][CH3:15])[C:11](=[O:16])[C:10]([C:17]3[N:21]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[N:20]=[CH:19][CH:18]=3)=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[NH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][C:30]1=[O:35].CNCCNC.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(O)=O.[Na+]>O1CCOCC1.[Cu]I>[F:28][C:3]1[C:2]([N:29]2[CH2:34][CH2:33][CH2:32][CH2:31][C:30]2=[O:35])=[CH:7][CH:6]=[CH:5][C:4]=1[N:8]1[CH:13]=[C:12]([O:14][CH3:15])[C:11](=[O:16])[C:10]([C:17]2[N:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:20]=[CH:19][CH:18]=2)=[N:9]1

Participants

8

Reactant 5

HCID 8070N,N'-DimethylethylenediamineHCID 126652-PiperidoneHCID 62657Potassium Phosphate, TribasicHCID 516892Sodium BicarbonateHCID 58072344HCID 58072344, compound

Product 1

HCID 580725031-[2-Fluoro-3-(2-oxopiperidin-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-oneYield 23%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of 1-(3-bromo-2-fluorophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (221 mg, 0.500 mmol), 2-piperidone (59.5 mg, 0.600 mmol), N,N′-dimethylethylenediamine (0.022 mL, 0.200 mmol), CuI (19 mg, 0.10 mmol) and K3PO4 (212 mg, 1.00 mmol) in 1,4-dioxane (2.0 mL) was stirred at 90° C. under Ar atmosphere. The reaction mixture was poured into 5% NaHCO3 aqueous solution (20 mL) and extracted with AcOEt (20 mL×3). The combined organic phase was washed with brine (40 mL), dried with MgSO4, and evaporated. The residue was purified by basic silica gel column chromatography (AcOEt/hexane=50%-100%) to give the title compound (52.3 mg, 23% yield) as an amorphous solid: 1H NMR (300 MHz, CDCl3): δ ppm 1.97 (4H, t, J=3.4 Hz), 2.54-2.63 (2H, m), 3.56 (2H, brs), 3.88 (3H, s), 6.36 (1H, dd, J=15.5, 1.9 Hz), 7.03 (1H, dd, J=16.2, 1.5 Hz), 7.22 (1H, dd, J=14.7, 1.9 Hz), 7.29 (1H, d, J=2.3 Hz), 7.35-7.44 (2H, m), 7.40 (3H, d, J=4.5 Hz), 7.78 (1H, d, J=1.9 Hz), 7.82 (1H, d, J=2.6 Hz). LC-MS (ESI) m/z 460 [M+H]+. Anal. Calcd for C25H22FN5O3.0.5H2O: C, 64.34; H, 4.93; N, 15.00. Found: C, 64.12; H, 4.73; N, 15.13.

Workup

  1. extractionextracted with AcOEt (20 mL×3)
  2. washThe combined organic phase was washed with brine (40 mL)
  3. dry with materialdried with MgSO4
  4. customevaporated
  5. customThe residue was purified by basic silica gel column chromatography (AcOEt/hexane=50%-100%)

Sources & evidence

ORD record
ord-0e4fb2327cb54142bd3c2ce4d4fb6bbb
Source dataset
uspto-grants-2013_08
Patent number
US08513251B2

Reaction notes

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