Cesium carbonate → Tert-butyl (4-(4-isopropylpiperazin-1-yl)-2-nitrophenyl)carbamate

HRID 58193Notes

Reaction equation

HRID 58193 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)([CH3:3])[CH3:2].Br[C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[C:13]([N+:25]([O-:27])=[O:26])[CH:12]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=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].O1CCOCC1.C1(C)C=CC=CC=1>[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[C:13]([N+:25]([O-:27])=[O:26])[CH:12]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 780131-IsopropylpiperazineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 52904808tert-Butyl (4-bromo-2-nitrophenyl)carbamate

Product 1

HCID 118034135Tert-butyl (4-(4-isopropylpiperazin-1-yl)-2-nitrophenyl)carbamateYield 70.5%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

1-isopropylpiperazine (1.29 g, 5.66 mmol) and tert-butyl (4-bromo-2-nitrophenyl)carbamate (1.5 g, 4.71 mmol) were taken in a mixture of dry toluene (15 mL) and dioxane (2 mL) in a seal tube under argon atmosphere at room temperature. The Argon gas was purged for 5-10 min. Then Cs2CO3 (3.06 g, 9.43 mmol) and Xantphos (0.54 g, 0.94 mmol) were added and the resulting reaction mixture was purged with argon gas for 5 min., followed by Pd2(dba)3 (0.43 g, 0.47 mmol). The argon gas purging was continued for additional 5 min. before sealing the reaction vial. Then the reaction mixture was heated at 100° C. for 12 hr. After completion of the reaction by TLC, the reaction mixture was cooled to room temperature, filtered through celite bed and concentrated. The residue was purified by silica gel column chromatography (DCM:MeOH/97:3) to afford the title compound (1.2 g, yield: 70.5%). MS (ESI): 365.5 [M+H]+.

Workup

  1. customThe Argon gas was purged for 5-10 min
  2. customthe resulting reaction mixture
  3. customwas purged with argon gas for 5 min.
  4. customThe argon gas purging
  5. customAfter completion of the reaction by TLC
  6. temperaturethe reaction mixture was cooled to room temperature
  7. filtrationfiltered through celite bed
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel column chromatography (DCM:MeOH/97:3)

Sources & evidence

ORD record
ord-d42be63aa535499088173e15186d4576
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Reaction notes

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