Cesium carbonate → 3-(6-chloro-8-oxo-8,9-dihydro-7H-purin-2-ylamino)-4-nitrobenzonitrile

HRID 600438Notes

Reaction equation

HRID 600438 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][C:7](=[O:11])[NH:8]2)=[C:4]([Cl:12])[N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][C:27]=1[N+:28]([O-:30])=[O:29])[C:23]#[N:24].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].C(O)C.O1CCOCC1>[Cl:12][C:4]1[N:3]=[C:2]([NH:1][C:26]2[CH:25]=[C:22]([CH:21]=[CH:20][C:27]=2[N+:28]([O-:30])=[O:29])[C:23]#[N:24])[N:10]=[C:9]2[C:5]=1[NH:6][C:7](=[O:11])[NH:8]2

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 184132163-Bromo-4-nitrobenzonitrileHCID 576126262-amino-6-chloro-7H-purin-8(9H)-one

Product 1

HCID 576127083-(6-chloro-8-oxo-8,9-dihydro-7H-purin-2-ylamino)-4-nitrobenzonitrileYield 46%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 702EthanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To an oven-dried microwave flask under Ar was added 2-amino-6-chloro-7H-purin-8(9H)-one (0.64 g, 3.46 mmol, 1.0 equiv.) followed by anhydrous dioxane (10 mL) and anhydrous ethanol (4 mL); Cs2CO3 (Aldrich, 2.25 g, 6.92 mmol, 2 equiv.), 3-bromo-4-nitro-benzonitrile (1.02 g, 4.5 mmol, 1.3 equiv.), Xantphos (Strem, 0.6 g, 1.04 mmol, 0.3 equiv.) and Pd2(dba)3 (Strem, 0.32 g, 0.35 mmol, 0.1 equiv.) were all added as solids, and the mixture was stirred under Ar, at room temperature for 3 min. The flask was capped and heated in the microwave at 140° C. for 150 min (LC-MS shows reaction to be complete). The reaction mixture was cooled to room temperature, then concentrated in vacuo to give a dark brown residue, which was purified by flash chromatography (silica gel, gradual elution 3/1 ethyl acetate/hexanes, then 4/1 ethyl acetate/hexanes with 1% MeOH to 20% MeOH) to give the desired product as an orange solid in 46% yield. 1H NMR (300 MHz, CD3COOD) δ, ppm: 9.31 (d, 1H), 8.36 (d, 1H), 7.43 (dd, 1H); MS (EI) m/z 332.0 (MH)+.

Workup

  1. additionall added as solids
  2. customThe flask was capped
  3. temperatureheated in the microwave at 140° C. for 150 min
  4. custom(LC-MS shows reaction to be complete)
  5. temperatureThe reaction mixture was cooled to room temperature
  6. concentrationconcentrated in vacuo
  7. customto give a dark brown residue, which
  8. customwas purified by flash chromatography (
  9. washsilica gel, gradual elution 3/1 ethyl acetate/hexanes

Sources & evidence

ORD record
ord-4cfc335002ba411586767c12a6b6bdd2
Source dataset
uspto-grants-2011_03
Patent number
US07902187B2

Reaction notes

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