Cesium carbonate → Methyl 3-(6-Chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)-1-methyl-1H-pyrazole-5-carboxylate

HRID 1918837Notes

Reaction equation

HRID 1918837 reaction equation
[NH2:1][C:2]1[CH:6]=[C:5]([C:7]([O:9][CH3:10])=[O:8])[N:4]([CH3:11])[N:3]=1.Br[C:13]1[C:14](=[O:21])[N:15]([CH3:20])[N:16]=[C:17]([Cl:19])[CH:18]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>>[Cl:19][C:17]1[CH:18]=[C:13]([NH:1][C:2]2[CH:6]=[C:5]([C:7]([O:9][CH3:10])=[O:8])[N:4]([CH3:11])[N:3]=2)[C:14](=[O:21])[N:15]([CH3:20])[N:16]=1

Participants

5

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 13248993methyl 3-amino-1-methyl-1H-pyrazole-5-carboxylateHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

Product 1

HCID 58043639Methyl 3-(6-Chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)-1-methyl-1H-pyrazole-5-carboxylate

Conditions

Temperature
100 °C

Procedure

In a 3-neck RBF was placed 119a (500 mg, 3.2 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (725 mg, 3.2 mmol), cesium carbonate (2.3 g, 7.0 mmol), and Xantphos (160 mg, 8.5 mol %). The flask was evacuated and filled with nitrogen 3×. Dioxane (20 ml) was added and the mixture degassed for 25 min with bubbling nitrogen. Tris(dibenzylideneacetone)dipalladium(0) (150 mg, 5 mol %) was then added and the reaction heated to 100° C. for 6 hrs. The reaction was cooled and diluted with EtOAc (125 mL) and saturated aqueous NaHCO3 (50 mL), the layers were separated and extracted EtOAc (2×100 mL). The organics were washed with brine 3×, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by chromatography: ISCO 40 g silica, EtOAc/hexanes, to give 119b.

Workup

  1. customThe flask was evacuated
  2. additionfilled with nitrogen 3×
  3. additionDioxane (20 ml) was added
  4. customthe mixture degassed for 25 min with bubbling nitrogen
  5. additionTris(dibenzylideneacetone)dipalladium(0) (150 mg, 5 mol %) was then added
  6. temperatureThe reaction was cooled
  7. additiondiluted with EtOAc (125 mL) and saturated aqueous NaHCO3 (50 mL)
  8. customthe layers were separated
  9. extractionextracted EtOAc (2×100 mL)
  10. washThe organics were washed with brine 3×
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by chromatography

Sources & evidence

ORD record
ord-d54723204ce54bd38693bd7b2a02b325
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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