Hydrochloric Acid → BF-844

HRID 1775588Notes

Reaction equation

HRID 1775588 reaction equation
[ClH:1].[N:2]([O-])=O.[Na+].[NH2:6][C:7]1[N:11]([CH2:12][C:13]([CH3:16])([OH:15])[CH3:14])[N:10]=[C:9]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:8]=1[C:23]#[C:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[Cl:1][C:23]1[C:24]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[N:2][N:6]=[C:7]2[N:11]([CH2:12][C:13]([CH3:16])([OH:15])[CH3:14])[N:10]=[C:9]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:8]=12

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 23668193Sodium NitriteHCID 70982768HCID 70982768, compound

Product 1

HCID 66576257BF-844

Procedure

To cooled (cooling bath −15° C.) conc. HCl (9 mL) was added sodium nitrite in one portion (121 mg, 1.75 mmol) and the suspension was left to stir for 10 min after which 1-(5-amino-3-phenyl-4-(phenylethynyl)-1H-pyrazol-1-yl)-2-methylpropan-2-ol (290 mg, 0.88 mmol) was added. After 5 min, the cooling bath was removed and the reaction mixture was stirred at room temperature for 3 h. The reaction was cooled again (0° C.) and DCM was added followed by water. The aqueous phase was extracted with DCM and the organic phases were combined, dried over MgSO4, filtered and evaporated. Crude material was purified by column chromatography (silica gel, gradient 0 to 50% ethyl acetate/isohexane) yielding 1-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)-2-methylpropan-2-ol as an orange oil (56 mg). The material obtained was further purified by preparative HPLC, yielding 34 mg of Compound 85 as a solid.

Workup

  1. waitthe suspension was left
  2. additionwas added
  3. customthe cooling bath was removed
  4. temperatureThe reaction was cooled again (0° C.) and DCM
  5. additionwas added
  6. extractionThe aqueous phase was extracted with DCM
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customCrude material was purified by column chromatography (silica gel, gradient 0 to 50% ethyl acetate/isohexane)

Sources & evidence

ORD record
ord-102d23f68bfc4d49a71851cc164e87c1
Source dataset
uspto-grants-2016_02
Patent number
US09260381B2

Reaction notes

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