Diisopropylamine → 2-Chloro-3-triethylsilylethynyl-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

HRID 2097511Notes

Reaction equation

HRID 2097511 reaction equation
[Cl:1][C:2]1[N:11]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:5]2[CH:6]=[N:7][NH:8][C:9](=[O:10])[C:4]=2[C:3]=1I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(NC(C)C)(C)C.[CH2:47]([Si:49]([C:54]#[CH:55])([CH2:52][CH3:53])[CH2:50][CH3:51])[CH3:48]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C)C=O>[Cl:1][C:2]1[N:11]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:5]2[CH:6]=[N:7][NH:8][C:9](=[O:10])[C:4]=2[C:3]=1[C:48]#[C:47][Si:49]([CH2:54][CH3:55])([CH2:52][CH3:53])[CH2:50][CH3:51]

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 11776TriphenylphosphineHCID 637947(Triethylsilyl)acetyleneHCID 666028262-Chloro-3-iodo-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

Product 1

HCID 666028662-Chloro-3-triethylsilylethynyl-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneYield 75%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To 61 mg (0.14 mmol) of 2-chloro-3-iodo-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Reference example 30-(b) were added 5 mg of bis(triphenylphosphine)palladium dichloride, 4 mg of cuprous iodide, 8 mg of triphenylphosphine, 1 ml of diisopropylamine, 0.04 ml of triethylsilylacetylene and 0.4 ml of N,N-dimethylformamide, the mixture was degassed under reduced pressure and replaced with argon, and the mixture was stirred at 80° C. for 1.5 hours. After completion of the reaction, toluene was added to the reaction mixture, and the mixture was washed successively with 5% aqueous sodium hydrogen sulfite solution, a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride. The organic layer after separation was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was applied to silica gel column chromatography (Eluent; hexane:ethyl acetate=7:3→1:1 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 47 mg of the title compound as a yellowish solid. (Yield: 75%)

Workup

  1. customthe mixture was degassed under reduced pressure
  2. customAfter completion of the reaction, toluene
  3. additionwas added to the reaction mixture
  4. washthe mixture was washed successively with 5% aqueous sodium hydrogen sulfite solution
  5. customThe organic layer after separation
  6. dry with materialwas dried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. additionthe fractions containing the desired compound
  9. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-c8ed12e5dfe747dda34481ab4c512a5a
Source dataset
uspto-grants-2013_05
Patent number
US08450319B2

Reaction notes

Loading…