4-Aminopyrimidine → 6-Chloro-3-methoxy-N-(pyrimidin-4-yl)pyridazin-4-amine

HRID 1907783Notes

Reaction equation

HRID 1907783 reaction equation
[Cl:1][C:2]1[N:7]=[N:6][C:5]([O:8][CH3:9])=[C:4](I)[CH:3]=1.[NH2:11][C:12]1[CH:17]=[CH:16][N:15]=[CH:14][N:13]=1.[O-]C1C=CC=CC=1.[Na+].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>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:1][C:2]1[N:7]=[N:6][C:5]([O:8][CH3:9])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][N:15]=[CH:14][N:13]=2)[CH:3]=1

Participants

6

Reactant 4

HCID 689584-AminopyrimidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 4445035Phenolate SodiumHCID 230924816-Chloro-4-iodo-3-methoxypyridazine

Product 1

HCID 585402886-Chloro-3-methoxy-N-(pyrimidin-4-yl)pyridazin-4-amine

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

In a dried pressure flask was placed compound 2 (1.0 g, 3.70 mmol), 4-aminopyrimidine (352 mg, 3.7 mmol), sodium phenoxide (860 mg, 7.4 mmol), Pd2(dba)3 (170 mg, 5 mol %), and Xantphos (150 mg, 7 mol %). The flask was evacuated and filled with N2 3× and then 20 mL anhydrous dioxane was added, The mixture was heated at 100° C. for 12 hours. The cooled mixture was diluted with ethyl acetate and water, filtered, separated, the ethyl acetate layer extracted 1× with ethyl acetate, the combined ethyl acetate layers washed with brine 4×, dried over Na2SO4, filtered and concentrated. The product was purified by column chromatography (silica) CH2Cl2/MeOH to give 3.

Workup

  1. customIn a dried pressure flask was placed
  2. customThe flask was evacuated
  3. additionfilled with N2 3×
  4. addition20 mL anhydrous dioxane was added
  5. additionThe cooled mixture was diluted with ethyl acetate and water
  6. filtrationfiltered
  7. customseparated
  8. extractionthe ethyl acetate layer extracted 1× with ethyl acetate
  9. washthe combined ethyl acetate layers washed with brine 4×
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe product was purified by column chromatography (silica) CH2Cl2/MeOH
  14. customto give 3

Sources & evidence

ORD record
ord-aa5417eaa2844ebf89d9d77360464d84
Source dataset
uspto-grants-2013_12
Patent number
US08598174B2

Reaction notes

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