Trifluoroacetic acid → 2-amino-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-one

HRID 600407Notes

Reaction equation

HRID 600407 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][C:7](=[O:17])[N:8]2[CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[C:4](Cl)[N:3]=1.[N:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(O)(C(F)(F)F)=O>CO.CC([O-])=O.CC([O-])=O.[Pd+2].O1CCOCC1.C(O)C>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][C:7](=[O:17])[N:8]2[CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[C:4]([C:22]2[CH:23]=[CH:24][N:19]=[CH:20][CH:21]=2)[N:3]=1

Participants

9

Reactant 4

HCID 6422Trifluoroacetic acidHCID 62657Potassium Phosphate, TribasicHCID 2734379(Pyridin-4-yl)boronic acidHCID 576126442-amino-6-chloro-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-one

Product 1

HCID 576126402-amino-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-oneYield 51.2%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

Anhydrous ethanol (2 mL) and anhydrous 1,4-dioxane (2 mL) were added to an argon-purged vial containing 2-amino-6-chloro-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-one (see preparation Route A, 100 mg, 0.37 mmol), pyridine-4-boronic acid (69 mg, 0.56 mmol, 1.5 equiv.), K3PO4 (157 mg, 0.74 mmol, 2.0 equiv.), Pd(OAc)2 (12.5 mg, 0.018 mmol, 0.05 equiv.) and D-tBPF 1,1′-bis(di-tbutylphosphino)ferrocene (8.8 mg, 0.018 mmol, 0.05 equiv.) and the mixture was heated for 2.5 h in the microwave oven at 150° C. After cooling to ambient temperature, the reaction mixture was diluted with methanol (20 mL), filtered through a Nylon 0.45 μm filter and the filtrate concentrated in vacuo. Preparative HPLC purification of the residue afforded, after evaporation and drying, the desired compound as a yellow solid (59.2 mg, 51% yield) TFA salt. 1H NMR (300 MHz, CD3OD) δ, ppm: 8.92 (d, J=6.4 Hz, 2H), 8.17 (dd, J=5.1, 1.5 Hz, 2H), 4.87-4.55 (m, 1H), 4.10 (dd, J=11.4, 4.3 Hz, 2H), 3.56 (ddd, J=11.3, 6.5, 4.7 Hz, 2H), 2.74 (tdd, J=12.6, 12.5, 4.6 Hz, 2H), 1.77 (dd, J=12.4, 2.4 Hz, 2H); MS (EI) m/z 313.3 (MH)+.

Workup

  1. custompurged vial
  2. temperatureAfter cooling to ambient temperature
  3. filtrationfiltered through a Nylon 0.45 μm
  4. filtrationfilter
  5. concentrationthe filtrate concentrated in vacuo
  6. customPreparative HPLC purification of the residue
  7. customafforded
  8. customafter evaporation
  9. customdrying

Sources & evidence

ORD record
ord-f107aa1aa6db4534933534d2fc26e2b8
Source dataset
uspto-grants-2011_03
Patent number
US07902187B2

Reaction notes

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