Toluene → 2-(3-Cyclopropoxy-4-difluoromethoxyphenyl)-3-methyl-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

HRID 2097375Notes

Reaction equation

HRID 2097375 reaction equation
Br[C:2]1[N:19]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:5]2[CH:6]=[N:7][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:9](=[O:10])[C:4]=2[C:3]=1[CH3:28].[CH:29]1([O:32][C:33]2[CH:34]=[C:35](B3OC(C)(C)C(C)(C)O3)[CH:36]=[CH:37][C:38]=2[O:39][CH:40]([F:42])[F:41])[CH2:31][CH2:30]1.C1(C)C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC.O>[CH:29]1([O:32][C:33]2[CH:34]=[C:35]([C:2]3[N:19]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:5]4[CH:6]=[N:7][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:16])[CH3:17])[C:9](=[O:10])[C:4]=4[C:3]=3[CH3:28])[CH:36]=[CH:37][C:38]=2[O:39][CH:40]([F:41])[F:42])[CH2:30][CH2:31]1

Participants

8

Reactant 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 666027042-Bromo-3-methyl-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneHCID 666028342-(3-Cyclopropoxy-4-difluoromethoxyphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane

Product 1

HCID 666028152-(3-Cyclopropoxy-4-difluoromethoxyphenyl)-3-methyl-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneYield 84.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneCatalystHCID 962WaterSolvent

Procedure

To a mixture of 1.46 g (3.00 mmol) of 2-bromo-3-methyl-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in the following Reference example 18-(d) and 1.47 g (4.50 mmol) of 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane obtained in the following Reference example 1-(a) were added 7 mg of palladium acetate, 22 mg of butyl-di-1-adamantylphosphine, 20 ml of toluene, 2.59 g of potassium phosphate and 1.2 ml of water, and the mixture was degassed under reduced pressure and replaced with argon. The reaction mixture was refluxed for 6 hours. After completion of the reaction, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer after separation was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The obtained residue was applied to silica gel column chromatography (Eluent; hexane:ethyl acetate=1:0→2:3 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 1.54 g of the title compound as a slightly yellowish oil. (Yield: 84%)

Workup

  1. customthe mixture was degassed under reduced pressure
  2. temperatureThe reaction mixture was refluxed for 6 hours
  3. customAfter completion of the reaction, water
  4. additionwas added to the reaction mixture
  5. extractionthe mixture was extracted with ethyl acetate
  6. customThe organic layer after separation
  7. washwas washed with a saturated aqueous solution of sodium chloride
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. additionthe fractions containing the desired compound
  11. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-7b84ae7341624911a462f4f7cd93ebfa
Source dataset
uspto-grants-2013_05
Patent number
US08450319B2

Reaction notes

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