Benzyl Bromide → 5-Benzyl-2-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-3-iodo-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

HRID 2097418Notes

Reaction equation

HRID 2097418 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([C:16]3[N:25]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:19]4[CH:20]=[N:21][NH:22][C:23](=[O:24])[C:18]=4[C:17]=3[I:34])[CH:9]=[CH:10][C:11]=2[O:12][CH:13]([F:15])[F:14])[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].[CH2:41](Br)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.[H-].[Na+].[Cl-].[NH4+]>CN(C)C=O>[CH2:41]([N:22]1[C:23](=[O:24])[C:18]2[C:17]([I:34])=[C:16]([C:8]3[CH:9]=[CH:10][C:11]([O:12][CH:13]([F:14])[F:15])=[C:6]([O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)[CH:7]=3)[N:25]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:31])([CH3:33])[CH3:32])[C:19]=2[CH:20]=[N:21]1)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

Participants

7

Reactant 5

HCID 7498Benzyl Bromide2×HCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 666028372-(3-Cyclopropylmethoxy-4-difluoromethoxyphenyl)-3-iodo-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

Product 1

HCID 666025865-Benzyl-2-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-3-iodo-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 452 mg (0.749 mmol) of 2-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-3-iodo-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Example 38-(b) and 126 mg of potassium carbonate was added 4 ml of dehydrated N,N-dimethylformamide, then 0.1 ml of benzyl bromide was added to the mixture, and the resulting mixture was stirred at room temperature for 16 hours. Moreover, 36 mg of sodium hydride (55% dispersed material in mineral oil) and 0.1 ml of benzyl bromide were further added to the mixture, and the resulting mixture was stirred for 2 hours. After completion of the reaction, a saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with toluene. The organic layer after separation was washed successively with water and then 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→1:1 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 389 mg of the title compound as a pale yellowish foam. (Yield: 75%)

Workup

  1. stirringthe resulting mixture was stirred for 2 hours
  2. customAfter completion of the reaction
  3. extractionthe mixture was extracted with toluene
  4. customThe organic layer after separation
  5. washwas washed successively with water
  6. dry with materialwith a saturated aqueous solution of sodium chloride, 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-2ed272a68e9840a6ad962f9caccda043
Source dataset
uspto-grants-2013_05
Patent number
US08450319B2

Reaction notes

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