Triphenylphosphine → tert-Butyl 4-(2-formyl-8-morpholinoimidazo[1,2-b]pyridazin-3-yl)benzoate

HRID 718570Notes

Reaction equation

HRID 718570 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]3[N:9]([CH:13]=[C:14]([CH:16]=[O:17])[N:15]=3)[N:10]=[CH:11][CH:12]=2)[CH2:3][CH2:2]1.[C:18]([O:22][C:23](=[O:31])[C:24]1[CH:29]=[CH:28][C:27](Br)=[CH:26][CH:25]=1)([CH3:21])([CH3:20])[CH3:19].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])(=O)C.[K+]>CN(C)C(=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:16]([C:14]1[N:15]=[C:8]2[C:7]([N:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)=[CH:12][CH:11]=[N:10][N:9]2[C:13]=1[C:27]1[CH:28]=[CH:29][C:24]([C:23]([O:22][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:31])=[CH:25][CH:26]=1)=[O:17]

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 517044Potassium AcetateHCID 11334366Tert-butyl 4-bromobenzoateHCID 1177286388-Morpholinoimidazo[1,2-b]pyridazine-2-carbaldehyde

Product 1

HCID 117732456tert-Butyl 4-(2-formyl-8-morpholinoimidazo[1,2-b]pyridazin-3-yl)benzoate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of compound 5e (0.57 g, 2.5 mmol), tert-butyl-4-bromobenzoate (0.97 g, 3.7 mmol), palladium acetate (38 mg, 0.17 mmol), triphenylphosphine (45 mg, 0.17 mmol) and potassium acetate (0.72 g, 7.3 mmol) were added while under an argon atmosphere and in dry N,N-dimethylacetamide (5 mL). The reaction mixture was stirred at 110° C. for 22 h, allowed to cool to rt, diluted with water (100 mL), and extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The obtained residue was purified by flash chromatography on silica gel (10-60% EtOAc/heptane) to give compound 5f as a pale yellow solid. 1H-NMR (400 MHz, CDCl3) δ (ppm): 10.13 (s, 1H), 8.13-8.21 (m, J=8.1 Hz, 2H), 8.09 (d, J=5.6 Hz, 1H), 7.85 (d, J=8.3 Hz, 2H), 6.15 (d, J=5.6 Hz, 1H), 4.02-4.14 (m, 4H), 3.90-4.00 (m, 4H), 1.62 (s, 9H).

Workup

  1. temperatureto cool to rt
  2. extractionextracted with EtOAc (2×100 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe obtained residue was purified by flash chromatography on silica gel (10-60% EtOAc/heptane)

Sources & evidence

ORD record
ord-e887cdb00cb9473e8c8b9f26ca76691a
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

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