Cesium carbonate → HCID 22396597, compound

HRID 1370462Notes

Reaction equation

HRID 1370462 reaction equation
C([O:5][C:6]([N:8]1[CH2:21][CH2:20][C:19]2[C:18]3[CH:17]=[C:16](B4OC(C)(C)C(C)(C)O4)[CH:15]=[CH:14][C:13]=3[NH:12][C:11]=2[CH2:10][CH2:9]1)=[O:7])(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.Br[C:39]1[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=1>C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2].CO.O1CCOCC1>[CH:6]([OH:7])=[O:5].[N:42]1[CH:43]=[CH:44][C:39]([C:16]2[CH:15]=[CH:14][C:13]3[NH:12][C:11]4[CH2:10][CH2:9][NH:8][CH2:21][CH2:20][C:19]=4[C:18]=3[CH:17]=2)=[CH:40][CH:41]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 881004-Bromopyridinium chlorideHCID 22396659HCID 22396659, compound

Product 1

HCID 22396597HCID 22396597, compoundYield 7%

Reagents, catalysts & solvents 2

HCID 15826098Cyclopenta-1,3-diene;cyclopenta-2,4-dien-1-yl(diphenyl)phosphane;iron(2+)CatalystHCID 21966525Dioxane MethanolSolvent

Conditions

Temperature
90 °C

Procedure

In a 20 mL vial a solution of MeOH/dioxane (10%, 1.5 mL, degassed with N2) was added to a mixture of 3-(tert-butyloxycarbonyl)-9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (0.097 g, 0.235 mmol), cesium carbonate (0.115 g, 0.35 mmol), and 4-bromopyridine hydrochloride (0.137 g, 0.70 mmol) and diphenylphosphinoferrocene (0.07 g, 5 mol %) were added. The mixture was flushed with argon and tris(dibenzylideneacetone)dipalladium (0) (0.06 g, 3 mol %) was added and the vial was placed on a shaker heated at 90° C. for 18 h. Equivalent amounts of cesium carbonate and the palladium catalyst were added with a small amount of MeOH for solubility, and the vial was returned to the shaker and heated at 90° C. for 48 h. MeOH and Bio-Rad Ag. 50W-X2 resin (0.8 g, 5.2 meq, 18 equivalents) were added and heated on the shaker at 65° C. for 2 h. The mixture was rinsed into a fritted plastic syringe and was washed with: MeOH, water, 2 N pyridine in MeOH, THF, MeOH, THF and finally CH2Cl2. The resulting cake of resin was then washed with 4 M NH4OH/MeOH and THF successively into tared vials, which were concentrated down on a Genevac for 18 h. The product was purified on a reverse phase HPLC system to give 4.3 mg (7%) of the title compound as the formate salt. MS (EI) m/z 264 (MH+).

Workup

  1. additionwere added
  2. customThe mixture was flushed with argon and tris(dibenzylideneacetone)dipalladium (0) (0.06 g, 3 mol %)
  3. additionwas added
  4. additionEquivalent amounts of cesium carbonate and the palladium catalyst were added with a small amount of MeOH for solubility
  5. temperatureheated at 90° C. for 48 h
  6. temperatureheated on the shaker at 65° C. for 2 h
  7. washThe mixture was rinsed into a fritted plastic syringe
  8. washwas washed with: MeOH, water, 2 N pyridine in MeOH, THF, MeOH, THF and finally CH2Cl2
  9. washThe resulting cake of resin was then washed with 4 M NH4OH/MeOH and THF successively into tared vials, which
  10. concentrationwere concentrated down on a Genevac for 18 h
  11. customThe product was purified on a reverse phase HPLC system

Sources & evidence

ORD record
ord-27f55ca5049a488eb19bc620262f03e0
Source dataset
uspto-grants-2003_06
Patent number
US06583135B2

Reaction notes

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