3-Pyrroline → HCID 58072184, compound

HRID 1895370Notes

Reaction equation

HRID 1895370 reaction equation
[F:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][C:3]=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.[NH:29]1[CH2:33][CH:32]=[CH:31][CH2:30]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC([O-])(C)C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[N:29]1([C:6]2[CH:5]=[CH:4][C:3]([N:9]3[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18]4[N:22]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[N:21]=[CH:20][CH:19]=4)=[N:10]3)=[C:2]([F:1])[CH:7]=2)[CH2:33][CH:32]=[CH:31][CH2:30]1

Participants

8

Reactant 4

HCID 660593-PyrrolineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 594362141-(2-fluoro-4-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Product 1

HCID 58072184HCID 58072184, compoundYield 51%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of 1-(2-fluoro-4-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (244 mg, 0.5 mmol), 3-pyrroline (0.046 mL, 0.6 mmol), Pd2(dba)3 (18.3 mg, 0.02 mmol), Xantphos (46.3 mg, 0.08 mmol), and NaOtBu (67.3 mg, 0.7 mmol) in 1,4-dioxane (2.5 mL) was stirred for 2 h at 90° C. under Ar atmosphere. The reaction mixture was poured into water and extracted with AcOEt. The extract was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography eluting with hexane/THF (1/2) and recrystallized from MeOH/H2O to give the title compound (109 mg, 51% yield) as a yellow solid: mp 204-207° C.; 1H NMR (300 MHz, CDCl3): δ ppm 3.89 (3H, s), 4.09 (4H, s), 5.97 (2H, t, J=4.1 Hz), 6.07 (1H, dd, J=2.6, 9.0 Hz), 6.19 (1H, dd, J=2.6, 14.3 Hz), 6.32 (1H, t, J=9.0 Hz), 7.24 (1H, d, J=1.9 Hz), 7.33-7.45 (5H, m), 7.72 (1H, d, J=2.3 Hz), 7.77 (1H, d, J=1.9 Hz). LC-MS (ESI) m/z 430 [M+H]+. Anal. Calcd for C24H20FN5O2: C, 67.12; H, 4.69; N, 16.31. Found: C, 67.03; H, 4.76; N, 16.16.

Workup

  1. extractionextracted with AcOEt
  2. washThe extract was washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by basic silica gel column chromatography
  6. washeluting with hexane/THF (1/2)
  7. customrecrystallized from MeOH/H2O

Sources & evidence

ORD record
ord-ce76780cbef24b429daf8823909f3e84
Source dataset
uspto-grants-2013_08
Patent number
US08513251B2

Reaction notes

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