2-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)acetaldehyde → 1-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)propan-2-ol

HRID 1775591Notes

Reaction equation

HRID 1775591 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:6][N:5]=[C:4]2[N:14]([CH2:23][CH:24]=[O:25])[N:15]=[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:3]=12.[CH3:26][Mg]Cl>C1COCC1>[Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[N:6][N:5]=[C:4]2[N:14]([CH2:23][CH:24]([OH:25])[CH3:26])[N:15]=[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:3]=12

Participants

4

Reactant 2

HCID 866970212-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)acetaldehydeHCID 178418332HCID 178418332, compound

Product 1

HCID 665763321-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)propan-2-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)acetaldehyde (128 mg, 0.29 mmol) in THF (2.9 mL) was added dropwise over 30 min to a solution of methyl magnesium chloride (290 μL of 3 M solution diluted in 2.9 mL THF) at 0° C. The crude mixture was partitioned between CH2Cl2 and 2 M hydrochloric acid. The aqueous phase was extracted with CH2Cl2 and the combined organic layers were passed over a phase separator and concentrated under reduced pressure. The reaction was repeated with another 80 mg of starting 2-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)acetaldehyde and the combined crude mixtures were purified by column chromatography (silica gel, gradient 50 to 100% ethyl acetate/isohexane). Additional preparative HPLC purification yielded 7.2 mg of Compound 91.

Workup

  1. customThe crude mixture was partitioned between CH2Cl2 and 2 M hydrochloric acid
  2. extractionThe aqueous phase was extracted with CH2Cl2
  3. concentrationconcentrated under reduced pressure
  4. customwere purified by column chromatography (silica gel, gradient 50 to 100% ethyl acetate/isohexane)
  5. customAdditional preparative HPLC purification

Sources & evidence

ORD record
ord-5441b8ec49c84a409a266c278fb88a3c
Source dataset
uspto-grants-2016_02
Patent number
US09260381B2

Reaction notes

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