Toluene → HCID 59393682, compound

HRID 2092136Notes

Reaction equation

HRID 2092136 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([C:20]3[CH:25]=[CH:24][C:23](B4OC(C)(C)C(C)(C)O4)=[CH:22][N:21]=3)([CH3:19])[CH:16]([CH3:18])[CH3:17])=[CH:11][CH:10]=2)[CH:6]=[N:7][CH:8]=1.[Cl:35][C:36]1[N:37]=[N:38][C:39](Cl)=[CH:40][CH:41]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>CCO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:35][C:36]1[N:37]=[N:38][C:39]([C:23]2[CH:22]=[N:21][C:20]([C:15]([C:12]3[CH:13]=[CH:14][C:9]([C:5]4[CH:6]=[N:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=4)=[CH:10][CH:11]=3)([CH3:19])[CH:16]([CH3:17])[CH3:18])=[CH:25][CH:24]=2)=[CH:40][CH:41]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 673313,6-DichloropyridazineHCID 59393696HCID 59393696, compound

Product 1

HCID 59393682HCID 59393682, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolvent

Conditions

Temperature
95 °C

Procedure

[1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (700 mg, 0.960 mmol) was added to a stirred solution of 4a (2.20 g, 4.80 mmol), 3,6-dichloropyridazine (1.40 g, 5.80 mmol) and sodium carbonate (4.80 mL of a 2.0 M aqueous solution, 9.60 mmol) in EtOH:toluene (25.0 mL of an 80:20 mixture, respectively) at rt. The resulting solution was heated to 95° C. for approximately 2 h. After cooling to rt, the reaction mixture was filtered through a short column of CELITE®, eluting with EtOAc. The filtrate was washed with water and brine, dried (sodium sulfate) and concentrated in vacuo. The crude residue was purified by flash chromatography on silica gel (gradient elution; 0%-60% EtOAc/hexanes as eluent) to furnish the title compound 4b. m/z (ES) 445 (MH)+. 1HNMR (500 MHz, CDCl3): δ 9.19 (d, 1H, J=2.1 Hz), 8.46 (d, 1H, J=1.6 Hz), 8.36 (dd, 1H, J=2.5, 8.5 Hz), 8.29 (d, 1H, J=2.8 Hz), 7.86 (d, 1H, J=8.9 Hz), 7.62 (d, 1H, J=8.9 Hz), 7.52 (m, 4H), 7.46 (d, 1H, J=8.2 Hz), 7.37 (m, 1H), 3.93 (s, 3H), 3.21 (m, 1H), 1.80 (s, 3H), 0.93 (d, 3H, J=6.9 Hz), 0.89 (d, 3H, J=6.9 Hz).

Workup

  1. customat rt
  2. temperatureAfter cooling to rt
  3. filtrationthe reaction mixture was filtered through a short column of CELITE®
  4. washeluting with EtOAc
  5. washThe filtrate was washed with water and brine
  6. dry with materialdried (sodium sulfate)
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was purified by flash chromatography on silica gel (gradient elution; 0%-60% EtOAc/hexanes as eluent)

Sources & evidence

ORD record
ord-ae918ff9f7694520a2a8dab06584e71b
Source dataset
uspto-grants-2013_05
Patent number
US08440672B2

Reaction notes

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