Sodium Hydroxide → Tert-butyl 5-(2,4-dichlorophenyl)-7-methyl-2-(3-methyl-1,2,4-oxadiazol-5-yl)imidazo[1,2-a]pyrimidine-6-carboxylate

HRID 1868475Notes

Reaction equation

HRID 1868475 reaction equation
[C:1]([C:4]1[N:5]=[C:6]2[N:11]=[C:10]([CH3:12])[C:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[C:8]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=3[Cl:27])[N:7]2[CH:28]=1)(=[O:3])[NH2:2].[CH3:29][C:30]([N:32](C)C)=O.CC(N(C)C)=O.NO.Cl.[OH-].[Na+]>C1(C)C=CC=CC=1.O1CCOCC1.CC(O)=O>[Cl:27][C:21]1[CH:22]=[C:23]([Cl:26])[CH:24]=[CH:25][C:20]=1[C:8]1[N:7]2[CH:28]=[C:4]([C:1]3[O:3][N:32]=[C:30]([CH3:29])[N:2]=3)[N:5]=[C:6]2[N:11]=[C:10]([CH3:12])[C:9]=1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 19097097DMA dimethylacetamideHCID 57982465Tert-butyl 2-carbamoyl-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-6-carboxylate

Product 1

HCID 57982492Tert-butyl 5-(2,4-dichlorophenyl)-7-methyl-2-(3-methyl-1,2,4-oxadiazol-5-yl)imidazo[1,2-a]pyrimidine-6-carboxylateYield 59%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of tert-butyl 2-carbamoyl-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-6-carboxylate (60 mg, 0.14 mmol) in PhCH3 (3 mL) was added DMA-DMA (70 μL, 0.43 mmol). The reaction was heated to 90° C. for 2 h and was concentrated to afford the crude ester as a black oil. This crude product was dissolved in dioxane (2 mL) and AcOH (2 mL) and NH2OH.HCl (15 mg, 0.21 mmol) was added followed by NaOH (2N solution, 0.1 mL, 0.2 mmol). After heating to 90° C. for 2 h, the reaction was concentrated under reduced pressure and diluted with EtOAc. The organic layer was washed with H2O and brine prior to drying over anhydrous MgSO4. Filtration, concentration under reduced pressure and purification by silica gel chromatography afforded tert-butyl 5-(2,4-dichlorophenyl)-7-methyl-2-(3-methyl-1,2,4-oxadiazol-5-yl)imidazo[1,2-a]pyrimidine-6-carboxylate (38 mg, 58%) as a yellow solid.

Workup

  1. concentrationwas concentrated
  2. customto afford the crude ester as a black oil
  3. temperatureAfter heating to 90° C. for 2 h
  4. concentrationthe reaction was concentrated under reduced pressure
  5. additiondiluted with EtOAc
  6. washThe organic layer was washed with H2O and brine
  7. dry with materialto drying over anhydrous MgSO4
  8. filtrationFiltration, concentration
  9. customunder reduced pressure and purification by silica gel chromatography

Sources & evidence

ORD record
ord-a908db72e12543cb96282f489a72b1e2
Source dataset
uspto-grants-2009_12
Patent number
US07635699B2

Reaction notes

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