Cesium carbonate → HCID 58247403, compound

HRID 2359660Notes

Reaction equation

HRID 2359660 reaction equation
Br[C:2]1[C:3]([O:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)=[N:4][C:5]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)=[N:6][CH:7]=1.[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24].C([O-])([O-])=O.[Cs+].[Cs+]>C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][N:33]([C:2]2[C:3]([O:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)=[N:4][C:5]([C:8]3[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=3)=[N:6][CH:7]=2)[CH2:32][CH2:31]1)=[O:29])([CH3:26])([CH3:24])[CH3:25]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 58247358HCID 58247358, compound

Product 1

HCID 58247403HCID 58247403, compoundYield 80.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 15826098Cyclopenta-1,3-diene;cyclopenta-2,4-dien-1-yl(diphenyl)phosphane;iron(2+)Catalyst

Conditions

Temperature
95 °C

Procedure

To a dry Schlenk tube was added a mixture of Compound 20d (100 mg; 0.28 mmol), piperazine-1-carboxylic acid tert-butyl ester (52 mg; 0.56 mmol), Cs2CO3 (227 mg; 0.70 mmol), (Diphenylphosphino)ferrocene (54 mg; 0.10 mmol), and Tris(dibenzylideneacetone)dipalladium(0) (25.6 mg; 0.028 mmol). Sealed the tube with a teflon-lined septum, evacuated, and refilled with argon. Added dioxane (0.3 mL; reaction conc. >0.75M) to the mixture via syringe. The mixture was heated at 95° C. for 3 h. Diluted the resulted mixture with EtOAc, washed with saturated NH4Cl(aq) and H2O. The organic phase was washed sequentially with H2O, and then dried over Na2SO4. The mixture was filtered and the filtrate was evaporated under reduced pressure to give the crude material. The crude material was purified by flash column chromatography (SiO2), eluting with a heptane-EtOAc gradient to afford Compound 20e (104 mg; 80% yield). 1H-NMR (400 MHz, CDCl3): δ 9.28 (d, 1H), 8.58 (dd, 1H), 8.35 (dt, 1H), 8.22 (s, 1H), 7.29 (td, 1H), 7.14 (dd, 2H), 6.98 (dd, 2H), 3.87 (s, 3H), 3.66 (t, 4H), 3.25 (t, 4H), 1.56 (s, 9H); MS: m/z 464.2 (M+H)+.

Workup

  1. additionTo a dry Schlenk tube was added
  2. customevacuated
  3. additionrefilled with argon
  4. additionDiluted the resulted mixture with EtOAc
  5. washwashed with saturated NH4Cl(aq) and H2O
  6. washThe organic phase was washed sequentially with H2O
  7. dry with materialdried over Na2SO4
  8. filtrationThe mixture was filtered
  9. customthe filtrate was evaporated under reduced pressure
  10. customto give the crude material
  11. customThe crude material was purified by flash column chromatography (SiO2)
  12. washeluting with a heptane-EtOAc gradient

Sources & evidence

ORD record
ord-f09a4c205d91446caadd81b115640eba
Source dataset
uspto-grants-2014_04
Patent number
US08685990B2

Reaction notes

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