2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → 5-(5-Bromo-2-chloropyrimidin-4-yl)-N-methyl-N-phenylthiazol-2-amine

HRID 2267383Notes

Reaction equation

HRID 2267383 reaction equation
[Li]C(C)(C)C.[CH3:6][N:7]([C:14]1[S:15][CH:16]=[CH:17][N:18]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[Br:19][C:20]1[CH:21]=[N:22][C:23]([Cl:26])=[N:24][CH:25]=1.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl.O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>CCOCC.O.C1COCC1>[Br:19][C:20]1[C:21]([C:16]2[S:15][C:14]([N:7]([CH3:6])[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)=[N:18][CH:17]=2)=[N:22][C:23]([Cl:26])=[N:24][CH:25]=1

Participants

9

Reactant 5

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 6066655-Bromo-2-chloropyrimidineHCID 234593752-(N-Methyl-N-phenylamino)thiazoleHCID 23667548Sodium AscorbateHCID 178418306HCID 178418306, compound

Product 1

HCID 602045055-(5-Bromo-2-chloropyrimidin-4-yl)-N-methyl-N-phenylthiazol-2-amine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

tBuLi (2.9 mL, 1.1 M solution in pentane, 3.0 mmol) was added to a stirred solution of 0.52 g (2.8 mmol) of 2-(N-Methyl-N-phenylamino)thiazole in 10 mL of Et2O at −78° C. The solution was stirred for 30 min at −78° C. before 0.59 g (3.0 mmol) of 5-bromo-2-chloropyrimidine and 10 mL of THF were added. The reaction solution was stirred for 30 min at −78° C., and then quenched by the addition of 5 mL of AcOH in 15 mL of MeOH. Solid 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (1.4 g, 6.1 mmol) was added and the reaction solution was warmed to 0° C. and stirred for 10 min, then poured into 100 mL of a 0.5 M solution of sodium ascorbate, diluted with 300 mL of water and the crude product removed by filtration and washed repeatedly with water. The residue was azeotroped with toluene and purified by flash chromatography eluting with a linear gradient of 10% EtOAc in hexane to 100% EtOAc to deliver the title compound. MS (M+H)+ 383.

Workup

  1. additionwere added
  2. customquenched by the addition of 5 mL of AcOH in 15 mL of MeOH
  3. temperaturethe reaction solution was warmed to 0° C.
  4. stirringstirred for 10 min
  5. customthe crude product removed by filtration
  6. washwashed repeatedly with water
  7. customThe residue was azeotroped with toluene
  8. custompurified by flash chromatography
  9. washeluting with a linear gradient of 10% EtOAc in hexane to 100% EtOAc

Sources & evidence

ORD record
ord-b780f0d4f15f46f8ba8141cea147c741
Source dataset
uspto-grants-2010_12
Patent number
US07858785B2

Reaction notes

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