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

HRID 2097398Notes

Reaction equation

HRID 2097398 reaction equation
[CH:1]1([O:4][C:5]2[CH:6]=[C:7]([C:15]3[N:31]([CH2:32]OCC[Si](C)(C)C)[C:18]4[CH:19]=[N:20][N:21](CC5C=CC=CC=5)[C:22](=[O:23])[C:17]=4[C:16]=3[OH:40])[CH:8]=[CH:9][C:10]=2[O:11][CH:12]([F:14])[F:13])[CH2:3][CH2:2]1.C1(O[C:45]2[CH:46]=[C:47](C3N(COCC[Si](C)(C)C)C4C=NNC(=O)C=4C=3)[CH:48]=[CH:49][C:50]=2OC(F)F)CC1>O>[CH:1]1([O:4][C:5]2[CH:6]=[C:7]([C:15]3[N:31]([CH2:32][C:45]4[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=4)[C:18]4[CH:19]=[N:20][NH:21][C:22](=[O:23])[C:17]=4[C:16]=3[OH:40])[CH:8]=[CH:9][C:10]=2[O:11][CH:12]([F:14])[F:13])[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 666024612-(3-Cyclopropoxy-4-difluoromethoxyphenyl)-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneHCID 666027512-(3-Cyclopropoxy-4-difluoromethoxyphenyl)-3-hydroxyphenylmethyl-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo-[2,3-d]pyridazin-4-one

Product 1

HCID 666023402-(3-Cyclopropoxy-4-difluoromethoxyphenyl)-3-hydroxyphenylmethyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneYield 42%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Reaction was carried out in the same manner as in Example 1-(b) except for using 51 mg (0.090 mmol) of 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-hydroxyphenylmethyl-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo-[2,3-d]pyridazin-4-one obtained in Example 20-(a) in place of 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one. After completion of the reaction, water was added to the reaction mixture, and the mixture was extracted with a mixed solvent (chloroform:methanol=9:1 (V/V)). The organic layer after separating the liquids was 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=9:1 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 17 mg of the title compound as a white solid. (Yield: 42%)

Workup

  1. customReaction
  2. additionwas added to the reaction mixture
  3. extractionthe mixture was extracted with a mixed solvent (chloroform:methanol=9:1 (V/V))
  4. customThe organic layer after separating the liquids
  5. dry with materialwas dried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. additionthe fractions containing the desired compound
  8. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-2f8795972973460d8e802f82fef0b5aa
Source dataset
uspto-grants-2013_05
Patent number
US08450319B2

Reaction notes

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