Pyridine → 4-{5-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyrimidin-2-yl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 1691879Notes

Reaction equation

HRID 1691879 reaction equation
[C:1]1([C:7]2[O:8][C:9]([C:15]([F:18])([F:17])[F:16])=[C:10]([C:12]([OH:14])=O)[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][N:35]([C:38]2[N:43]=[CH:42][C:41]([NH2:44])=[CH:40][N:39]=2)[CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O>[C:25]([O:29][C:30]([N:32]1[CH2:33][CH2:34][N:35]([C:38]2[N:43]=[CH:42][C:41]([NH:44][C:12]([C:10]3[N:11]=[C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[O:8][C:9]=3[C:15]([F:18])([F:17])[F:16])=[O:14])=[CH:40][N:39]=2)[CH2:36][CH2:37]1)=[O:31])([CH3:28])([CH3:26])[CH3:27]

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 27764382-Phenyl-5-(trifluoromethyl)-oxazole-4-carboxylic acidHCID 594643191,1-Dimethylethyl 4-(5-amino-2-pyrimidinyl)-1-piperazinecarboxylate

Product 1

HCID 667384454-{5-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyrimidin-2-yl}-piperazine-1-carboxylic acid tert-butyl esterYield 88.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 2-phenyl-5-trifluoromethyloxazole-4-carboxylic acid (771 mg, 3 mmol) in methylene chloride (10 mL) was added oxalyl chloride (2M, 3 mL, 6.0 mmol) and one drop of N,N-dimethylformamide. The mixture was stirred at room temperature for 1 hr and the solvents were evaporated. The residue was treated with benzene (5 mL) and the solvents were again evaporated. The oily residue was dried in vacuum and then dissolved in methylene chloride (10 mL). The solution was cooled in an ice bath. To this solution was added a methylene chloride solution of 4-(5-amino-pyrimidin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester (3 mmol) and pyridine (0.73 mL). The mixture was stirred at 0° C. for 10 minutes and room temperature for 2 hrs. After concentration, the residue was partitioned between methylene chloride and water. The organic layer was washed with aqueous citric acid solution and dried over sodium sulfate. The solvents were evaporated and the residue was dried in vacuum. The resulting material was triturated with ethyl acetate and the precipitate was filtered to give 4-{5-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyrimidin-2-yl}-piperazine-1-carboxylic acid tert-butyl ester (1.38 g). LC-MS calcd for C24H25F3N6O4 (m/e) 518.5, obsd 519.1 (M+H). The NMR spectrum obtained on the sample is compatible with its structure.

Workup

  1. customthe solvents were evaporated
  2. additionThe residue was treated with benzene (5 mL)
  3. customthe solvents were again evaporated
  4. customThe oily residue was dried in vacuum
  5. dissolutiondissolved in methylene chloride (10 mL)
  6. temperatureThe solution was cooled in an ice bath
  7. stirringThe mixture was stirred at 0° C. for 10 minutes and room temperature for 2 hrs
  8. concentrationAfter concentration
  9. customthe residue was partitioned between methylene chloride and water
  10. washThe organic layer was washed with aqueous citric acid solution
  11. dry with materialdried over sodium sulfate
  12. customThe solvents were evaporated
  13. customthe residue was dried in vacuum
  14. customThe resulting material was triturated with ethyl acetate
  15. filtrationthe precipitate was filtered

Sources & evidence

ORD record
ord-a83171f6d46949919ce9d677e1a103bf
Source dataset
uspto-grants-2012_04
Patent number
US08153644B2

Reaction notes

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