Cesium carbonate → HCID 178518647, compound

HRID 600453Notes

Reaction equation

HRID 600453 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][C:7](=[O:18])[N:8]2[C@H:11]2[CH2:16][CH2:15][C@H:14]([OH:17])[CH2:13][CH2:12]2)=[C:4]([Cl:19])[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.Br[C:73]1[CH:78]=[C:77]([F:79])[CH:76]=[CH:75][C:74]=1[N+:80]([O-:82])=[O:81]>CC([O-])=O.CC([O-])=O.[Pd+2].C1(C)C=CC=CC=1>[Cl:19][C:4]1[N:3]=[C:2]([NH:1][C:73]2[CH:78]=[C:77]([F:79])[CH:76]=[CH:75][C:74]=2[N+:80]([O-:82])=[O:81])[N:10]=[C:9]2[C:5]=1[NH:6][C:7](=[O:18])[N:8]2[C@H:11]1[CH2:12][CH2:13][C@H:14]([OH:17])[CH2:15][CH2:16]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 27569932-Bromo-4-fluoro-1-nitrobenzeneHCID 178508437HCID 178508437, compound

Product 1

HCID 178518647HCID 178518647, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

All glassware was dried in vacuum oven at 60° C. for 1 day prior to reaction. Finely ground cesium carbonate and finely ground 2-amino-6-chloro-9-(trans-4-hydroxycyclohexyl)-7H-purin-8(9H)-one were dried at 60° C. under high vacuum for one day prior to experiment. To an oven-dried 2-neck flask under Ar was added 2-amino-6-chloro-9-(trans-4-hydroxycyclohexyl)-7H-purin-8(9H)-one (6.78 g, 23.9 mmol), cesium carbonate (11.71 g, 35.9 mmol, 1.5 equiv.) and anhydrous toluene (100 mL) and the mixture was stirred at room temperature for 15 min. Then, Pd(OAc)2 (2.41 g, 3.59 mmol, 0.15 equiv.), racemic BINAP (5.21 g, 8.36 mmol, 0.35 equiv.) and 1-bromo-5-fluoro-2-nitrobenzene (6.84 g, 31.07 mmol, 1.3 equiv.) were added as solids, under Ar, and the reaction mixture was stirred at room temperature for 15 min, then stirred at 100° C. for 2 days (LC-MS shows ratio of desired product/starting material approx. 8/1). The reaction mixture was cooled to room temperature, and the solvent removed in vacuo. The dark brown residue was dissolved in warm CH3COOH/EtOH (60 mL/60 mL), and then water (700 mL) was added. A dark yellow solid precipitated and was filtered under vacuum. A small portion of the dark yellow solid was purified by flash chromatography (silica gel, gradient elution with ethyl acetate/hexanes 1/1 to 3/1, then up to 20% methanol in 3/1 ethyl acetate/hexanes) to provide the desired compound as an orange solid. 1H NMR (300 MHz, CDCl3+CD3OD) δ, ppm: 10.67 (br s, 1H), 8.80 (dd, 1H), 8.37 (dd, 1H), 6.85-6.80 (m, 1H), 4.39-4.30 (m, 1H), 3.81-3.73 (m, 1H), 2.67-2.44 (m, 2H), 2.18-2.14 (m, 2H), 1.92-1.88 (m, 2H), 1.56-1.41 (m, 2H); MS (EI) m/z 423.3 (MH)+.

Workup

  1. customAll glassware was dried in vacuum oven at 60° C. for 1 day
  2. customto reaction
  3. dry with materialFinely ground cesium carbonate and finely ground 2-amino-6-chloro-9-(trans-4-hydroxycyclohexyl)-7H-purin-8(9H)-one were dried at 60° C. under high vacuum for one day
  4. stirringthe reaction mixture was stirred at room temperature for 15 min
  5. stirringstirred at 100° C. for 2 days (LC-MS shows ratio of desired product/starting material approx. 8/1)
  6. temperatureThe reaction mixture was cooled to room temperature
  7. customthe solvent removed in vacuo
  8. dissolutionThe dark brown residue was dissolved in warm CH3COOH/EtOH (60 mL/60 mL)
  9. additionwater (700 mL) was added
  10. customA dark yellow solid precipitated
  11. filtrationwas filtered under vacuum
  12. customA small portion of the dark yellow solid was purified by flash chromatography (
  13. washsilica gel, gradient elution with ethyl acetate/hexanes 1/1 to 3/1

Sources & evidence

ORD record
ord-457be52819654eb586b79c7a863c1c97
Source dataset
uspto-grants-2011_03
Patent number
US07902187B2

Reaction notes

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