Toluene → HCID 57910808, compound

HRID 1968669Notes

Reaction equation

HRID 1968669 reaction equation
[CH3:1][C:2]([C:21]1[CH:26]=[CH:25][C:24]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=2)=[CH:23][N:22]=1)([C:6]1[CH:11]=[CH:10][C:9](B2OC(C)(C)C(C)(C)O2)=[CH:8][CH:7]=1)[CH:3]([CH3:5])[CH3:4].[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:9]2[CH:10]=[CH:11][C:6]([C:2]([CH3:1])([C:21]3[CH:26]=[CH:25][C:24]([O:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=4)=[CH:23][N:22]=3)[CH:3]([CH3:4])[CH3:5])=[CH:7][CH:8]=2)=[CH:40][CH:41]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 673313,6-DichloropyridazineHCID 579107912-{1,2-Dimethyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propyl}-5-(pyridin-2-ylmethoxy)pyridine

Product 1

HCID 57910808HCID 57910808, 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) (69.0 mg, 0.0950 mmol) was added to a stirred solution of 5a (1.45 g, 3.16 mmol), 3,6-dichloropyridazine (660 mg, 4.43 mmol) and sodium carbonate (3.20 mL of a 2.0 M aqueous solution, 6.32 mmol) in EtOH:toluene (10.0 mL of an 80:20 mixture, respectively) at rt. The resulting solution was heated to 95° C. for approximately 4 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, brine, dried (sodium sulfate) and concentrated in vacuo. The crude residue was purified by flash chromatography on silica gel (gradient elution; 20%-80% EtOAc/hexanes as eluent) to furnish the title compound 5b. m/z (ES) 445 (MH)+. 1HNMR (500 MHz, CDCl3): δ 8.63 (d, 1H, J=4.1 Hz), 8.41 (d, 1H, J=1.8 Hz), 7.96 (d, 2H, J=8.7 Hz), 7.80 (d, 1H, J=8.9 Hz), 7.76 (dt, 1H, J=1.7, 7.7 Hz), 7.53 (m, 4H), 7.27 (dd, 1H, J=5.1, 7.1 Hz), 7.19 (m, 2H), 5.24 (s, 2H), 3.11 (m, 1H, J=6.7 Hz), 1.61 (s, 3H), 0.89 (d, 3H, J=6.6 Hz), 0.83 (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, 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; 20%-80% EtOAc/hexanes as eluent)

Sources & evidence

ORD record
ord-37fb4b4f967142788c9f01bf2fda0b98
Source dataset
uspto-grants-2013_04
Patent number
US08426413B2

Reaction notes

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