Potassium Acetate → 6-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

HRID 1621357Notes

Reaction equation

HRID 1621357 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.[F:18][C:19]1[C:24](B(O)O)=[CH:23][CH:22]=[CH:21][N:20]=1.C([O-])(=O)C.[K+]>CCO.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[F:18][C:19]1[C:24]([C:2]2[N:10]=[C:9]([CH3:11])[N:8]=[C:7]3[C:3]=2[N:4]=[CH:5][N:6]3[CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)=[CH:23][CH:22]=[CH:21][N:20]=1

Participants

6

Reactant 3

HCID 517044Potassium AcetateHCID 27832702-Fluoropyridine-3-boronic acidHCID 595482686-chloro-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Product 1

HCID 595484686-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purineYield 78.7%

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 702EthanolSolvent

Procedure

A mixture of 6-chloro-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (3) (531.6 mg, 2104 μmol), 2-fluoropyridin-3-ylboronic acid (Asymchem Laboratories, Inc., Morrisville, N.C.) (596 mg, 4230 μmol), potassium acetate (629 mg, 6409 μmol) and bis(di-tert-butyl (4-dimethylaminophenyl)phosphine)dichloropalladium(II) (Aldrich, St. Louis, Mo.) (37.2 mg, 52.6 μmol) under a N2 atmosphere was suspended in EtOH (5.0 mL) and H2O (1.0 mL), degassed, and heated at gentle reflux for 2 h. LCMS indicated the reaction was complete. The mixture was poured into saturated aqueous NaHCO3 and extracted into EtOAc. The EtOAc extracts were dried (MgSO4), concentrated and purified by flash chromatography (EtOAc) to give 6-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (519 mg, 78.7% yield) as a pale yellow oil which crystallized to give a white solid upon trituration with Et2O. 1H NMR (400 MHz, d6-DMSO) δ 8.79 (s, 1H); 8.46-8.53 (m, 1H); 8.43-8.46 (m, 1H); 7.55-7.62 (m, 1H); 5.78-5.85 (m, 1H); 4.00-4.08 (m, 1H); 3.70-3.80 (m, 1H); 2.78 (s, 3H); 2.26-2.40 (m, 1H); 1.95-2.06 (m, 2H); 1.72-1.87 (m, 1H); 1.56-1.67 (m, 2H). m/z (ESI, +ve) 314.0 (M+H)+.

Workup

  1. customH2O (1.0 mL), degassed
  2. temperatureheated
  3. temperatureat gentle reflux for 2 h
  4. additionThe mixture was poured into saturated aqueous NaHCO3
  5. extractionextracted into EtOAc
  6. dry with materialThe EtOAc extracts were dried (MgSO4)
  7. concentrationconcentrated
  8. custompurified by flash chromatography (EtOAc)

Sources & evidence

ORD record
ord-dd39642b3a8e416085079a214da371f9
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

Loading…