Potassium Phosphate, Tribasic → 3-Methyl-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

HRID 2097493Notes

Reaction equation

HRID 2097493 reaction equation
[CH:1]1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.I[C:31]1[C:39]2[C:38](=[O:40])[N:37]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[N:36]=[CH:35][C:34]=2[N:33]([CH2:49][O:50][CH2:51][CH2:52][Si:53]([CH3:56])([CH3:55])[CH3:54])[CH:32]=1.CB(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1.O1CCCC1>[CH3:1][C:31]1[C:39]2[C:38](=[O:40])[N:37]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[N:36]=[CH:35][C:34]=2[N:33]([CH2:49][O:50][CH2:51][CH2:52][Si:53]([CH3:56])([CH3:55])[CH3:54])[CH:32]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 139377Methylboronic AcidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 666025043-Iodo-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

Product 1

HCID 666025023-Methyl-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneYield 917.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

1 ml of tetrahydrofuran was added to 34 mg (0.15 mmol) of palladium acetate and 126 mg (0.306 mmol) of 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl, the mixture was degassed under reduced pressure and replaced with argon. Then, the mixture was stirred at room temperature for 30 minutes. Thereafter, 1.59 g (3.04 mmol) of 3-iodo-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Reference example 18-(b), 551 mg (9.20 mmol) of methylboronic acid, 2.62 g (12.3 mmol) of potassium phosphate and 9 ml of toluene were added to the mixture, and after the resulting mixture was again degassed under reduced pressure and replaced with argon, the mixture was stirred at 100° C. for 4 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=19:1→3:2 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 1.15 g of the title compound as a yellowish solid. (Yield: 92%)

Workup

  1. customthe mixture was degassed under reduced pressure
  2. customafter the resulting mixture was again degassed under reduced pressure
  3. stirringthe mixture was stirred at 100° C. for 4 hours
  4. customAfter completion of the reaction, water
  5. additionwas added to the reaction mixture
  6. extractionthe mixture was extracted with ethyl acetate
  7. customThe organic layer after separation
  8. washwas washed with a saturated aqueous solution of sodium chloride
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. additionthe fractions containing the desired compound
  12. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-0000bdb1a74b490bb315dc283ff7dad1
Source dataset
uspto-grants-2013_05
Patent number
US08450319B2

Reaction notes

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