Dimethylacetamide → tert-butyl 1-(4-(8-cyano-4-oxo-2-phenyl-4H-pyrano[2,3-c]pyridin-3-yl)phenyl)cyclobutylcarbamate

HRID 1037429Notes

Reaction equation

HRID 1037429 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.C1(C2C3C(=CC=CC=3)C=CC=2)C2C(=CC=CC=2)C=CC=1.C(PC(C)(C)C)(C)(C)C.C[C:67]([N:69](C)C)=O>[C-]#N.[Zn+2].[C-]#N.FC(F)(F)C([O-])=O.[Pd+2].FC(F)(F)C([O-])=O.[Zn]>[C:67]([C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[C:11](=[O:12])[C:10]([C:13]3[CH:14]=[CH:15][C:16]([C:19]4([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:20][CH2:21][CH2:22]4)=[CH:17][CH:18]=3)=[C:9]([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[O:8][C:7]=12)#[N:69]

Participants

7

Reactant 3

HCID 31374DimethylacetamideHCID 66906061HCID 66906061, compoundHCID 86671031tert-Butyl 1-(4-(8-chloro-4-oxo-2-phenyl-4H-pyrano[2,3-c]pyridin-3-yl)phenyl)cyclobutylcarbamate

Product 1

HCID 68227519tert-butyl 1-(4-(8-cyano-4-oxo-2-phenyl-4H-pyrano[2,3-c]pyridin-3-yl)phenyl)cyclobutylcarbamateYield 61%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 2733347Palladium(II) trifluoroacetateCatalyst

Conditions

Temperature
95 °C

Procedure

tert-Butyl (1-(4-(8-chloro-4-oxo-2-phenyl-4H-pyrano[2,3-c]pyridin-3-yl)phenyl)cyclobutyl)carbamate (50 mg, 0.1 mmol), zinc (II) cyanide (38 mg, 0.058 mmol) and binaphthyl-di-tert-butyl phosphine (4 mg, 0.01 mmol), palladium(II) trifluoroacetate (4 mg, 0.01 mmol), zinc dust (2 mg) were suspended in DMA (1 mL) in a microwave vial. The vial was sealed, evacuated and flushed twice with nitrogen. The reaction mixture was heated at 95° C. for 18 h. The resulting mixture was allowed to cool to RT, partitioned between ethyl acetate (40 mL) and water (20 mL) and the phases were separated. The organic layer was washed with brine (2 mL), dried (Na2SO4), filtered and concentrated in vacuo. The resulting residue was subjected to flash chromatography (SiO2, 50% ethyl acetate in cyclohexane) to afford the title compound (30 mg, 61%). LCMS (Method I): RT=7.63 min, [M+H]+=438 (-tBu), [M+Na]+=516.

Workup

  1. customThe vial was sealed
  2. customevacuated
  3. customflushed twice with nitrogen
  4. temperatureto cool to RT
  5. custompartitioned between ethyl acetate (40 mL) and water (20 mL)
  6. customthe phases were separated
  7. washThe organic layer was washed with brine (2 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-71677fc2a6bd4113bb0aaf2119b02cc4
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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