Imidazole → tert-butyl (1-(4-(8-(1H-imidazol-1-yl)-4-oxo-2-phenyl-4H-pyrano[2,3-c]pyridin-3-yl)phenyl)cyclobutyl)carbamate

HRID 1037415Notes

Reaction equation

HRID 1037415 reaction equation
Cl[C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[C:11](=[O:12])[C:10]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:22][CH2:21][CH2:20]4)=[CH:15][CH:14]=3)=[C:9]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[O:8][C:7]=12.[NH:37]1[CH:41]=[CH:40][N:39]=[CH:38]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.[Cu](I)I>[N:37]1([C:2]2[N:3]=[CH:4][CH:5]=[C:6]3[C:11](=[O:12])[C:10]([C:13]4[CH:14]=[CH:15][C:16]([C:19]5([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:28])([CH3:27])[CH3:29])[CH2:22][CH2:21][CH2:20]5)=[CH:17][CH:18]=4)=[C:9]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[O:8][C:7]=23)[CH:41]=[CH:40][N:39]=[CH:38]1

Participants

6

Reactant 3

HCID 795ImidazoleHCID 10796Cesium carbonateHCID 86671031tert-Butyl 1-(4-(8-chloro-4-oxo-2-phenyl-4H-pyrano[2,3-c]pyridin-3-yl)phenyl)cyclobutylcarbamate

Product 1

HCID 86671059tert-butyl (1-(4-(8-(1H-imidazol-1-yl)-4-oxo-2-phenyl-4H-pyrano[2,3-c]pyridin-3-yl)phenyl)cyclobutyl)carbamateYield 32.5%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

tert-Butyl (1-(4-(8-chloro-4-oxo-2-phenyl-4H-pyrano[2,3-c]pyridin-3-yl)phenyl)cyclobutyl)carbamate (63 mg, 0.115 mmol), imidazole (11 mg, 0.161 mmol), cesium carbonate (75 mg, 0.23 mmol) and copper (II) iodide (5 mg, 0.023 mmol) were dissolved in DMF (1 mL) in a microwave vial. The vial was sealed, evacuated and flushed twice with nitrogen. The reaction mixture was heated conventionally at 120° C. for 72 h. After cooling to RT, the resultant mixture was diluted with EtOAc, washed with water, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, 1:1 ethyl acetate/hexane) to give the title compound (20 mg, 24%). LCMS (Method I): RT=5.89 min, [M+H]+=535.

Workup

  1. customThe vial was sealed
  2. customevacuated
  3. customflushed twice with nitrogen
  4. temperatureAfter cooling to RT
  5. additionthe resultant mixture was diluted with EtOAc
  6. washwashed with water
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2a240891743d460790235ccbf6d7658a
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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