Methanol → 2-Chloro-8-methoxy-9-(tetrahydro-2H-pyran-4-ylmethyl)-9H-Purin-6-amine

HRID 1010975Notes

Reaction equation

HRID 1010975 reaction equation
Br[C:2]1[N:3]([CH2:13][CH:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:4]2[C:9]([N:10]=1)=[C:8]([NH2:11])[N:7]=[C:6]([Cl:12])[N:5]=2.[OH-:20].[Na+].[CH3:22]O>CO.CS(C)=O>[Cl:12][C:6]1[N:5]=[C:4]2[C:9]([N:10]=[C:2]([O:20][CH3:22])[N:3]2[CH2:13][CH:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[C:8]([NH2:11])[N:7]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 576996638-Bromo-2-chloro-9-(tetrahydro-2H-pyran-4-ylmethyl)-9H-Purin-6-amine

Product 1

HCID 576997442-Chloro-8-methoxy-9-(tetrahydro-2H-pyran-4-ylmethyl)-9H-Purin-6-amine

Reagents, catalysts & solvents 1

HCID 22036561Dimethyl sulfoxide methanolSolvent

Procedure

To a solution of 8-bromo-2-chloro-9-(tetrahydro-2H-pyran-4-ylmethyl)-9H-purin-6-amine (1.36 g) in dry MeOH (27.5 mL) was added 1M sodium hydroxide solution (27.5 mL) and the mixture was stirred at reflux for 30 mins. The reaction was cooled to room temperature and concentrated in vacuo. The residue obtained was triturated with water (60 mL) and extracted with EtOAc (120 mL). The organic layer was washed with brine (60 mL), dried over MgSO4, filtered and concentrated in vacuo to give a pink/white solid. The material was taken up in MeOH/DMSO (1:1) and a precipitate crashed out of solution. The solid was filtered off and the filtrate was purified by C18 reverse phase chromatography (ISCO) using water (0.1% formic acid)-acetonitrile (0.05% formic acid) as eluent (10-45%). The filtered solid was combined with the material obtained from the purification to give the title compound (192 mg).

Workup

  1. temperatureat reflux for 30 mins
  2. concentrationconcentrated in vacuo
  3. customThe residue obtained
  4. customwas triturated with water (60 mL)
  5. extractionextracted with EtOAc (120 mL)
  6. washThe organic layer was washed with brine (60 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a pink/white solid
  11. filtrationThe solid was filtered off
  12. customthe filtrate was purified by C18 reverse phase chromatography (ISCO)
  13. customobtained from the purification

Sources & evidence

ORD record
ord-9a2eaaefe6b14a548e828aa4bee99548
Source dataset
uspto-grants-2011_07
Patent number
US07977344B2

Reaction notes

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