Diethyl Ether → 6-Chloro-4-(5-(2-hydroxypropan-2-yl)-1-methyl-1H-pyrazol-3-ylamino)-2-methylpyridazin-3(2H)-one

HRID 1918838Notes

Reaction equation

HRID 1918838 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14](C(OC)=O)[N:13]([CH3:20])[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[CH2:21]1COCC1.C[Mg]Br.C([O:31][CH2:32][CH3:33])C>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([C:32]([OH:31])([CH3:33])[CH3:21])[N:13]([CH3:20])[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 8028TetrahydrofuranHCID 58043639Methyl 3-(6-Chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)-1-methyl-1H-pyrazole-5-carboxylateHCID 178418573HCID 178418573, compound

Product 1

HCID 580442586-Chloro-4-(5-(2-hydroxypropan-2-yl)-1-methyl-1H-pyrazol-3-ylamino)-2-methylpyridazin-3(2H)-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-25 °C

Procedure

In a 100 mL round bottom flask containing 119b (500 mg, 1.7 mmol) under nitrogen was added anh. THF (20 mL) and anh.toluene (5 mL) and the mixture stirred and cooled to −20 to −30° C. 3.0M methylmagnesium bromide in diethylether (1.6 mL, 4.75 mmol) was then slowly added. After the addition the reaction was allowed to slowly warm to room temp. and stir for about 3 hrs after which the reaction was quenched with 1N HCl. Concentrated to remove THF, diluted with ethyl acetate and water then adjusted the pH to ˜6-7 with 1M NaOH. Separated and extracted 2× with ethyl acetate washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by chromatography: ISCO 24 g silica, ethyl acetate/hexanes, to give 119c.

Workup

  1. additionAfter the addition the reaction
  2. temperatureto slowly warm to room temp.
  3. customwas quenched with 1N HCl
  4. concentrationConcentrated
  5. customto remove THF
  6. additiondiluted with ethyl acetate and water
  7. customSeparated
  8. extractionextracted 2× with ethyl acetate
  9. washwashed with brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified by chromatography

Sources & evidence

ORD record
ord-7ab97bfdeaf84368ad23e8b057447ab8
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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