Sodium Bicarbonate → 2-(2-Cyclopropyl-8-difluoromethoxy-2H-chromen-5-yl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

HRID 2097440Notes

Reaction equation

HRID 2097440 reaction equation
[CH:1]1([CH:4]2[CH:13]=[CH:12][C:11]3[C:6](=[C:7]([O:32][CH:33]([F:35])[F:34])[CH:8]=[CH:9][C:10]=3[C:14]3[N:23](COCC[Si](C)(C)C)[C:17]4[CH:18]=[N:19][NH:20][C:21](=[O:22])[C:16]=4[CH:15]=3)[O:5]2)[CH2:3][CH2:2]1.C1(OC2C=C(C3N(COCC[Si](C)(C)C)C4C=NNC(=O)C=4C=3)C=CC=2OC(F)F)CCC1.C(=O)([O-])O.[Na+]>>[CH:1]1([CH:4]2[CH:13]=[CH:12][C:11]3[C:6](=[C:7]([O:32][CH:33]([F:34])[F:35])[CH:8]=[CH:9][C:10]=3[C:14]3[NH:23][C:17]4[CH:18]=[N:19][NH:20][C:21](=[O:22])[C:16]=4[CH:15]=3)[O:5]2)[CH2:2][CH2:3]1

Participants

4

Reactant 3

HCID 516892Sodium BicarbonateHCID 666026362-(3-Cyclobutoxy-4-difluoromethoxyphenyl)-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneHCID 666031022-(2-cyclopropyl-8-difluoromethoxy-2H-chromen-5-yl)-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

Product 1

HCID 1356204832-(2-Cyclopropyl-8-difluoromethoxy-2H-chromen-5-yl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneYield 56.4%

Procedure

Reaction was carried out in the same manner as in Example 31-(b) except for using 194 mg (0.387 mmol) of 2-(2-cyclopropyl-8-difluoromethoxy-2H-chromen-5-yl)-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Example 58-(a) in place of 2-(3-cyclobutoxy-4-difluoromethoxyphenyl)-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one. After completion of the reaction, the reaction mixture was neutralized with a saturated aqueous solution of sodium hydrogencarbonate and the mixture was extracted with a mixed solvent (chloroform/methanol=9/1 (V/V)). 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. To the obtained solid were added methanol and 28% aqueous ammonia, and the mixture was stirred under room temperature for 3 hours. Then, the solution was concentrated under reduced pressure and the obtained residue was applied to silica gel column chromatography (Eluent; chloroform:methanol=9:1 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 81 mg of the title compound as a white solid. (Yield: 56%)

Workup

  1. customReaction
  2. customAfter completion of the reaction
  3. extractionthe mixture was extracted with a mixed solvent (chloroform/methanol=9/1 (V/V))
  4. customThe organic layer after separation
  5. washwas washed with a saturated aqueous solution of sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. additionTo the obtained solid were added methanol and 28% aqueous ammonia
  9. concentrationThen, the solution was concentrated under reduced pressure
  10. additionthe fractions containing the desired compound
  11. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-9641c9b5ea594c10b0e4687440377401
Source dataset
uspto-grants-2013_05
Patent number
US08450319B2

Reaction notes

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