Cesium carbonate → HCID 66600008, compound

HRID 1811902Notes

Reaction equation

HRID 1811902 reaction equation
Cl[C:2]1[N:10]=[C:9]([CH3:11])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1.[Cl:18][C:19]1[CH:24]=[CH:23][N:22]=[CH:21][C:20]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.[Pd+2].ClC1C=C[C-](P(C2C=CC=CC=2)C2C=CC=CC=2)C=1Cl.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:18][C:19]1[CH:24]=[CH:23][N:22]=[CH:21][C:20]=1[C:2]1[N:10]=[C:9]([CH3:11])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 120670644-Chloropyridine-3-boronic acid, pinacol esterHCID 595482686-chloro-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Product 1

HCID 66600008HCID 66600008, compoundYield 15%

Reagents, catalysts & solvents 3

HCID 178478230HCID 178478230, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-chloro-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (506 mg, 2.004 mmol), 4-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (480 mg, 2.004 mmol, Combi-Blocks, Inc., San Diego, Calif.), dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium (II) (164 mg, 0.200 mmol), and cesium carbonate (0.321 mL, 4.01 mmol) in dioxane (4 mL) and water (0.5 mL) was stirred at 100° C. for 30 min. The mixture was cooled down to room temperature. The reaction mixture was diluted with water (5 mL) and extracted with EtOAc (2×30 mL), The organic extract was washed with saturated NaCl (2 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give a yellow solid. The crude material was adsorbed onto a plug of silica gel and purified by flash chromatography eluting with 10% MeOH in CH2Cl2 to provide 6-(4-chloropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (98 mg, 15% yield) as light-yellow glass. 1H NMR (300 MHz, CDCl3) δ 8.83 (s, 1H); 8.61 (d, J=5.41 Hz, 1H); 8.27 (s, 1H); 7.50 (d, J=5.41 Hz, 1H); 5.87 (d, J=10.08 Hz, 1H); 4.20 (d, J=11.25 Hz, 1H); 3.84 (t, J=11.33 Hz, 1H); 3.48 (d, J=5.41 Hz, 1H); 2.90 (s, 3H); 1.99-2.29 (m, 3H); 1.64-1.95 (m, 3H). m/z (ESI, +ve ion) 330 (M+H)+.

Workup

  1. temperatureThe mixture was cooled down to room temperature
  2. extractionextracted with EtOAc (2×30 mL)
  3. extractionThe organic extract
  4. washwas washed with saturated NaCl (2 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto give a yellow solid
  9. custompurified by flash chromatography
  10. washeluting with 10% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-f829229d7f2b410a9baa2025db700362
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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