2-tert-Butyl-1,3-diisopropylisourea → 4-(4-Bromo-2-fluoro-phenylamino)-6-chloro-pyridazine-3-carboxylic acid tert-butyl ester

HRID 558225Notes

Reaction equation

HRID 558225 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[CH:14]=[C:13]([Cl:15])[N:12]=[N:11][C:10]=2[C:16]([OH:18])=[O:17])=[C:4]([F:19])[CH:3]=1.[C:20](OC(=NC(C)C)NC(C)C)([CH3:23])([CH3:22])[CH3:21]>C1COCC1.C(OCC)(=O)C>[C:20]([O:17][C:16]([C:10]1[N:11]=[N:12][C:13]([Cl:15])=[CH:14][C:9]=1[NH:8][C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=1[F:19])=[O:18])([CH3:23])([CH3:22])[CH3:21]

Participants

5

Reactant 2

HCID 110417822-tert-Butyl-1,3-diisopropylisoureaHCID 595194954-(4-Bromo-2-fluoro-phenylamino)-6-chloro-pyridazine-3-carboxylic acid

Product 1

HCID 595194124-(4-Bromo-2-fluoro-phenylamino)-6-chloro-pyridazine-3-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To the stirred solution of 4-(4-bromo-2-fluoro-phenylamino)-6-chloro-pyridazine-3-carboxylic acid (516 gm, 1.49 mmol) in THF (10 ml) under argon at room temperature is added a solution of 2-tert-butyl-1,3-diisopropylisourea (1.49 g, 7.45 mmol) in THF (1.0 ml). The resulted mixture is refluxed for 6 hours. The reaction mixture is then cooled to room temperature and diluted with ethyl acetate. The organic layer is washed with 10% K2CO3 (20 ml×2) and saturated NaCl (30 ml×3), dried over Na2SO4 and concentrated in vacuum. The residue is dissolved in 30 ml of dichloromethane and the resulting white solid (urea byproduct) is filtered out. The filtrate is concentrated under reduced pressure. The residue is purified by flash column chromatography to provide the desired product.

Workup

  1. temperatureThe resulted mixture is refluxed for 6 hours
  2. washThe organic layer is washed with 10% K2CO3 (20 ml×2) and saturated NaCl (30 ml×3)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuum
  5. dissolutionThe residue is dissolved in 30 ml of dichloromethane
  6. filtrationthe resulting white solid (urea byproduct) is filtered out
  7. concentrationThe filtrate is concentrated under reduced pressure
  8. customThe residue is purified by flash column chromatography

Sources & evidence

ORD record
ord-fa42588b75c34dd88cb403894a876780
Source dataset
uspto-grants-2011_11
Patent number
US08063049B2

Reaction notes

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