1H-1,2,4-Triazole → {1-[4-(4-oxo-2-phenyl-8-[1,2,4]triazol-4-yl-4H-pyrano[2,3-c]pyridin-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 1037399Notes

Reaction equation

HRID 1037399 reaction equation
[C:1]([O:5][C:6](=[O:36])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19](=[O:35])[C:20]4[C:21]([O:27][C:28]=3[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[C:22](Cl)[N:23]=[CH:24][CH:25]=4)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[NH:37]1[CH:41]=[N:40][CH:39]=[N:38]1.C(=O)([O-])[O-].[Cs+].[Cs+]>[Cu]I.CN1C(=O)CCC1>[C:1]([O:5][C:6](=[O:36])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19](=[O:35])[C:20]4[C:21]([O:27][C:28]=3[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[C:22]([N:40]3[CH:39]=[N:38][N:37]=[CH:41]3)[N:23]=[CH:24][CH:25]=4)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 92571H-1,2,4-Triazole2×HCID 10796Cesium carbonate2×HCID 86671031tert-Butyl 1-(4-(8-chloro-4-oxo-2-phenyl-4H-pyrano[2,3-c]pyridin-3-yl)phenyl)cyclobutylcarbamate2×

Product 1

HCID 67067789{1-[4-(4-oxo-2-phenyl-8-[1,2,4]triazol-4-yl-4H-pyrano[2,3-c]pyridin-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl esterYield 185.3%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
150 °C

Procedure

To a microwave vial were added {1-[4-(8-chloro-4-oxo-2-phenyl-4H-pyrano[2,3-c]pyridin-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (6.7 mg, 0.0133 mmol), 1,2,4-triazole (4.6 mg, 0.067 mmol), cesium carbonate (8.7 mg, 0.0266 mmol), copper(I) iodide (0.8 mg, 0.004 mmol) and NMP (0.5 mL). The reaction mixture was heated in a microwave reactor at 150° C. for 30 minutes. The reaction was repeated with {1-[4-(8-chloro-4-oxo-2-phenyl-4H-pyrano[2,3-c]pyridin-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (20 mg, 0.04 mmol), 1,2,4-triazole (13.8 mg, 0.2 mmol), cesium carbonate (26.1 mg, 0.08 mmol), copper(I) iodide (2.4 mg, 0.012 mmol) and NMP (0.7 mL). The reaction mixtures were combined and partitioned between EtOAc and water. The organic phase was extracted further with EtOAc and the combined organic extracts were washed with water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 50 to 75% EtOAc in cyclohexane) to afford the title compound (13.2 mg, 46%) as a colourless gum. LCMS (Method H): RT=3.84 min, [M+H]+=536.

Workup

  1. customThe reaction mixtures
  2. custompartitioned between EtOAc and water
  3. extractionThe organic phase was extracted further with EtOAc
  4. washthe combined organic extracts were washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-eb43603044d748f591ab61b62727cf24
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

Loading…