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

HRID 507614Notes

Reaction equation

HRID 507614 reaction equation
[Li]C(C)(C)C.[F:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14]2[S:15][CH:16]=[CH:17][N:18]=2)=[CH:9][CH:8]=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+]>CCCCCCC.C1COCC1.O.CO>[Br:19][C:20]1[C:21]([C:16]2[S:15][C:14]([NH:13][C:10]3[CH:9]=[CH:8][C:7]([F:6])=[CH:12][CH:11]=3)=[N:18][CH:17]=2)=[N:22][C:23]([Cl:26])=[N:24][CH:25]=1

Participants

10

Reactant 5

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 6066655-Bromo-2-chloropyrimidineHCID 23667548Sodium AscorbateHCID 25093329N-(4-Fluorophenyl)thiazol-2-amineHCID 178418306HCID 178418306, compound

Product 1

HCID 602045115-(5-Bromo-2-chloropyrimidin-4-yl)-N-(4-fluorophenyl)thiazol-2-amine

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8900HeptaneSolvent

Conditions

Temperature
0 °C

Procedure

8.1 mL (12 mmol) of a 1.5 M solution of tBuLi in heptane was added to a stirred solution of 1.1 g (5.5 mmol) of N-(4-fluorophenyl)thiazol-2-amine in 20 mL of THF at −20° C. The solution was stirred for 30 min and then cooled to −78° C. before 1.3 g (6.6 mmol) of 5-bromo-2-chloropyrimidine was added. The reaction solution was stirred for 30 min at −78° C., then quenched by addition of 0.2 mL of AcOH in 1 mL of MeOH. Solid 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (10.4 g, 46 mmol) and 5 mL of MeOH were added and the reaction solution was warmed to 0° C. and stirred for 30 min, poured into 50 mL of a 0.5 M solution of sodium ascorbate, diluted with 200 mL of water and the crude product removed by filtration and washed repeatedly with water. The crude product was purified by flash chromatography eluting with a linear gradient of 10% EtOAc in hexane to 80% EtOAc in hexane to deliver the desired compound. MS (M+H)+ 387.

Workup

  1. additionwas added
  2. stirringThe reaction solution was stirred for 30 min at −78° C.
  3. customquenched by addition of 0.2 mL of AcOH in 1 mL of MeOH
  4. stirringstirred for 30 min
  5. customthe crude product removed by filtration
  6. washwashed repeatedly with water
  7. customThe crude product was purified by flash chromatography
  8. washeluting with a linear gradient of 10% EtOAc in hexane to 80% EtOAc in hexane

Sources & evidence

ORD record
ord-10dfa063618d4a41b1277ac58fccf8cd
Source dataset
uspto-grants-2010_08
Patent number
US07786132B2

Reaction notes

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