Cesium carbonate → 9-(8-Aza-bicyclo[3.2.1]oct-3-ylidene)-5-phenyl-9H-xanthene-3-carboxylic acid diethylamide

HRID 733066Notes

Reaction equation

HRID 733066 reaction equation
[CH2:1]([N:3]([CH2:29][CH3:30])[C:4]([C:6]1[CH:7]=[CH:8][C:9]2[C:10](=[C:21]3[CH2:27][CH:26]4[NH:28][CH:23]([CH2:24][CH2:25]4)[CH2:22]3)[C:11]3[C:16]([O:17][C:18]=2[CH:19]=1)=[C:15](Br)[CH:14]=[CH:13][CH:12]=3)=[O:5])[CH3:2].[C:31]1(B(O)O)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:1]([N:3]([CH2:29][CH3:30])[C:4]([C:6]1[CH:7]=[CH:8][C:9]2[C:10](=[C:21]3[CH2:27][CH:26]4[NH:28][CH:23]([CH2:24][CH2:25]4)[CH2:22]3)[C:11]3[C:16]([O:17][C:18]=2[CH:19]=1)=[C:15]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH:14]=[CH:13][CH:12]=3)=[O:5])[CH3:2]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 66827Phenylboronic AcidHCID 469179409-(8-Aza-bicyclo[3.2.1]oct-3-ylidene)-5-bromo-9H-xanthene-3-carboxylic acid diethylamide

Product 1

HCID 469179959-(8-Aza-bicyclo[3.2.1]oct-3-ylidene)-5-phenyl-9H-xanthene-3-carboxylic acid diethylamideYield 90.7%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 9-(8-aza-bicyclo[3.2.1]oct-3-ylidene)-5-bromo-9H-xanthene-3-carboxylic acid diethylamide (0.170, 0.363 mmol), phenylboronic acid (0.049 g, 0.40 mmol) and cesium carbonate (0.236 g, 0.726 mmol) in dioxane (4 mL) and ethanol (1 mL) was treated with dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (13 mg), and the resulting mixture was heated at reflux for 2 h. The reaction mixture was cooled to room temperature, and the inorganics removed by filtration and washed successively with dioxane, ethanol and dichloromethane. The solvents were evaporated in vacuo. The residue was purified by reverse phase (C18) preparative HPLC, using a gradient of acetonitrile (10% to 90%) in water with trifluoroacetate (0.1%) as the eluant to give the title compound (0.153 g) as a colorless solid. MS: m/z 465.3 (MH+). 1H NMR (DMSO-d6): δ 1.05-1.20 (br m, 6 H0, 1.31 d, 2 H, J=8.2 Hz), 1.75-1.85 (br m, 2 H), 2.90-3.10 (m, 4 H), 3.15-3.50 (br m, 4 H), 4.03 br s, 2 H), 7.10 (d, 1 H, J=1.5 Hz), 7.20 (d of d, 1 H, J=1.5 & 7.9 Hz), 7.32 (t, 1 H, J=7.5 Hz), 7.40-7.63 (m, 8 H), 8.83 (br s, 1 H0 and 9.16 (br d, 1 H).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureat reflux for 2 h
  3. customthe inorganics removed by filtration
  4. washwashed successively with dioxane, ethanol and dichloromethane
  5. customThe solvents were evaporated in vacuo
  6. customThe residue was purified by reverse phase (C18) preparative HPLC

Sources & evidence

ORD record
ord-692ed06fd5dd4552ad240132f16026cd
Source dataset
uspto-grants-2009_09
Patent number
US07589103B2

Reaction notes

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