Diisopropyl Ether → 3-Chloro-2-(3-cyclobutoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

HRID 2097412Notes

Reaction equation

HRID 2097412 reaction equation
[Cl:1][C:2]1[C:10]2[C:9](=[O:11])[NH:8][N:7]=[CH:6][C:5]=2[N:4](COCC[Si](C)(C)C)[C:3]=1[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH:27]([F:29])[F:28])=[C:22]([O:30][CH:31]2[CH2:34][CH2:33][CH2:32]2)[CH:21]=1.ClC1C2C(=O)NN=CC=2N(COCC[Si](C)(C)C)C=1C1C=CC(OC(F)F)=C(OC2CC2)C=1.C(OC(C)C)(C)C>C1CCCCC1>[Cl:1][C:2]1[C:10]2[C:9](=[O:11])[NH:8][N:7]=[CH:6][C:5]=2[NH:4][C:3]=1[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH:27]([F:29])[F:28])=[C:22]([O:30][CH:31]2[CH2:32][CH2:33][CH2:34]2)[CH:21]=1

Participants

5

Reactant 3

HCID 7914Diisopropyl EtherHCID 666026323-Chloro-2-(3-cyclobutoxy-4-difluoromethoxyphenyl)-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneHCID 666026343-Chloro-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

Product 1

HCID 1358450613-Chloro-2-(3-cyclobutoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneYield 62%

Reagents, catalysts & solvents 1

HCID 8078CyclohexaneSolvent

Procedure

Reaction was carried out in the same manner as in Example 2-(b) except for using 0.26 g (0.51 mmol) of 3-chloro-2-(3-cyclobutoxy-4-difluoromethoxyphenyl)-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Example 32-(a) in place of 3-chloro-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one. After completion of the reaction, to the reaction mixture were added diisopropyl ether and cyclohexane, and the precipitated solid was collected by filtration and washed with cyclohexane. To the obtained solid were added methanol and 28% aqueous ammonia, and the mixture was stirred at room temperature for 3 hours. Then, the solution was concentrated under reduced pressure, and the obtained solid was washed with chloroform and dried under reduced pressure to obtain 120 mg of the title compound as a white solid. (Yield: 62%)

Workup

  1. customReaction
  2. customAfter completion of the reaction
  3. filtrationthe precipitated solid was collected by filtration
  4. washwashed with cyclohexane
  5. additionTo the obtained solid were added methanol and 28% aqueous ammonia
  6. concentrationThen, the solution was concentrated under reduced pressure
  7. washthe obtained solid was washed with chloroform
  8. customdried under reduced pressure

Sources & evidence

ORD record
ord-50069cf3777d460fb275e6507529306f
Source dataset
uspto-grants-2013_05
Patent number
US08450319B2

Reaction notes

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