Ammonium Chloride → 2-(3-Cyclopropoxy-4-difluoromethoxyphenyl)-3-(1-hydroxy-2-propynyl)-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

HRID 2097456Notes

Reaction equation

HRID 2097456 reaction equation
[CH:1]1([O:4][C:5]2[CH:6]=[C:7]([C:15]3[N:32]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[C:18]4[CH:19]=[N:20][N:21]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:22](=[O:23])[C:17]=4[C:16]=3[CH:41]=[O:42])[CH:8]=[CH:9][C:10]=2[O:11][CH:12]([F:14])[F:13])[CH2:3][CH2:2]1.[C:43]([Mg]Br)#[CH:44].[Cl-].[NH4+]>O1CCCC1>[CH:1]1([O:4][C:5]2[CH:6]=[C:7]([C:15]3[N:32]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[C:18]4[CH:19]=[N:20][N:21]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:29])[CH3:30])[C:22](=[O:23])[C:17]=4[C:16]=3[CH:41]([OH:42])[C:43]#[CH:44])[CH:8]=[CH:9][C:10]=2[O:11][CH:12]([F:13])[F:14])[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 86627032HCID 86627032, compoundHCID 178418486HCID 178418486, compound

Product 1

HCID 866270332-(3-Cyclopropoxy-4-difluoromethoxyphenyl)-3-(1-hydroxy-2-propynyl)-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To 25 ml of tetrahydrofuran solution containing 1.01 g (1.62 mmol) of 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-formyl-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in the same manner as in Example 15-(a) was added dropwise 3.6 ml of tetrahydrofuran solution containing 0.5M ethynyl magnesium bromide at 60° C., and the mixture was stirred at the same temperature for 30 minutes. After completion of the reaction, the reaction mixture was poured into a saturated ammonium chloride solution, and 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=7:3 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 1.11 g of the title compound as a yellowish oil. (Yield: 96%)

Workup

  1. customobtained in the same manner as in Example 15-(a)
  2. customAfter completion of the reaction
  3. extractionextracted 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-fb70c8c60d094baeabbc19f295851194
Source dataset
uspto-grants-2013_05
Patent number
US08450319B2

Reaction notes

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