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

HRID 1407366Notes

Reaction equation

HRID 1407366 reaction equation
Br[C:2]1[C:7]([F:8])=[CH:6][C:5]([N:9]2[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18]3[N:22]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[N:21]=[CH:20][CH:19]=3)=[N:10]2)=[C:4]([F:29])[CH:3]=1.[NH:30]1[CH2:34][CH2:33][CH2:32][C:31]1=[O:35].CNCCNC.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.[Cu]I>[F:29][C:4]1[CH:3]=[C:2]([N:30]2[CH2:34][CH2:33][CH2:32][C:31]2=[O:35])[C:7]([F:8])=[CH:6][C:5]=1[N:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18]2[N:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:21]=[CH:20][CH:19]=2)=[N:10]1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 120252-PyrrolidoneHCID 62657Potassium Phosphate, TribasicHCID 580724211-(4-Bromo-2,5-difluorophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Product 1

HCID 580721981-[2,5-Difluoro-4-(2-oxopyrrolidin-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-oneYield 6%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

A suspension of 1-(4-bromo-2,5-difluorophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (200 mg, 0.44 mmol), pyrrolidin-2-one (0.040 mL, 0.53 mmol), CuI (17 mg, 0.088 mmol), N,N′-dimethylethane-1,2-diamine (0.019 mL, 0.18 mmol), and K3PO4 (187 mg, 0.88 mmol) in 1,4-dioxane (4.0 mL) was stirred at 80° C. for 14 h under N2 atmosphere. After cooling to rt, the reaction mixture was purified by silica gel column chromatography eluting with hexane/AcOEt (1/0 to 0/1) then AcOEt/MeOH (10/1) and recrystallized from AcOEt to give the title compound (12 mg, 6% yield) as a pale brown solid: 1H NMR (300 MHz, DMSO-d6): δ ppm 2.06-2.23 (2H, m), 3.29 (3H, s), 3.69-3.91 (4H, m), 7.27-7.42 (2H, m), 7.43-7.56 (2H, m), 7.78 (1H, dd, J=11.3, 6.4 Hz), 7.85-7.91 (2H, m), 7.95 (1H, dd, J=10.5, 7.2 Hz), 8.57 (1H, d, J=2.3 Hz), 8.60 (1H, d, J=1.5 Hz). LC-MS (ESI) m/z 464 [M+H]+.

Workup

  1. temperatureAfter cooling to rt
  2. customthe reaction mixture was purified by silica gel column chromatography
  3. washeluting with hexane/AcOEt (1/0 to 0/1)
  4. customAcOEt/MeOH (10/1) and recrystallized from AcOEt

Sources & evidence

ORD record
ord-b7b10f99fb9748628035e4059ec437ca
Source dataset
uspto-grants-2014_12
Patent number
US08916566B2

Reaction notes

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