Hydrochloric Acid → HCID 67426864, compound

HRID 888969Notes

Reaction equation

HRID 888969 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]([CH3:11])[N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[Cl:24])[N:6]2[CH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.[CH2:25]([N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)[CH3:26].C(N(CC)CC)C.Cl>C(O)C.C(OCC)C>[ClH:1].[Cl:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:5]1[N:6]([CH:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:7]2[C:3]([N:4]=1)=[C:2]([N:30]1[CH2:31][CH2:32][N:27]([CH2:25][CH3:26])[CH2:28][CH2:29]1)[N:10]=[C:9]([CH3:11])[N:8]=2

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 791961-EthylpiperazineHCID 59374608HCID 59374608, compound

Product 1

HCID 67426864HCID 67426864, compoundYield 83.8%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

Heat a solution of 6-chloro-8-(2-chlorophenyl)-2-methyl-9-(tetrahydro-2H-pyran-4-yl)-9H-purine (0.0005 mol, 0.2 g), N-ethyl piperazine (0.0006 mol, 0.069 g, 1.1 equiv.), and triethylamine (0.0006 mol, 0.061 g, 1.1 equiv.) in ethanol (5.0 mL) at reflux for 20 hours. Alternatively, heat the reaction with microwave irradiation. Upon reaction completion, concentrate the reaction mixture under reduced pressure. Dissolve the residue in dry dichloromethane and wash with saturated sodium bicarbonate solution, water, and brine. Dry the organic layer over anhydrous sodium sulfate, filter, and concentrate under reduced pressure to give the residue. Purify by silica gel chromatography eluting with hexanes:acetone 90:10 to give the freebase. Add HCl (2M solution in ethanol) (1.0 equiv.) to the freebase (0.23 g, 0.500 mmol) in diethyl ether (5 mL) at 0° C. and stir for 2 hours at room temperature. Filter and wash precipitate with diethyl ether. Dry the precipitate under vacuum to give the title compound (0.2 g). MS (m/z): 441.28 (M+1). Alternatively, prepare the HCl salt by dissolving the freebase in acetone, 1:1 acetonitrile:water, or another suitable organic solvent, then add with stirring a solution of aqueous or ethereal HCl. Then lyophilize to afford the hydrochloride salt.

Workup

  1. temperatureat reflux for 20 hours
  2. temperatureAlternatively, heat
  3. customthe reaction
  4. customwith microwave irradiation
  5. customUpon reaction completion
  6. concentrationconcentrate the reaction mixture under reduced pressure
  7. dissolutionDissolve the residue in dry dichloromethane
  8. washwash with saturated sodium bicarbonate solution, water, and brine
  9. dry with materialDry the organic layer over anhydrous sodium sulfate
  10. filtrationfilter
  11. concentrationconcentrate under reduced pressure
  12. customto give the residue
  13. customPurify by silica gel chromatography
  14. washeluting with hexanes:acetone 90:10
  15. customto give the freebase
  16. filtrationFilter
  17. washwash precipitate with diethyl ether
  18. customDry the precipitate under vacuum

Sources & evidence

ORD record
ord-b0ab4e57996c4102a82ba2e310e5a2bf
Source dataset
uspto-grants-2012_08
Patent number
US08252798B2

Reaction notes

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