Water → HCID 44248021, compound

HRID 1010926Notes

Reaction equation

HRID 1010926 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[NH:19]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11].C(=O)([O-])[O-].[K+].[K+].Br[CH2:32][CH:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1.O>CN(C=O)C>[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[N:19]2[CH2:32][CH:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27732864-(Bromomethyl)oxaneHCID 178450370HCID 178450370, compound

Product 1

HCID 44248021HCID 44248021, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Butoxy-8-methoxy-9H-purin-6-amine trifluoroacetate salt (0.5 g) was heated to 60° C. for 1 hour with anhydrous potassium carbonate (0.79 g) in dry DMF (10 mL) and allowed to cool to room temperature before adding 4-(bromomethyl)tetrahydro-2H-pyran (0.26 g). The reaction was stirred at room temperature for 39 hours and heated for 2 hours at 50° C. The reaction was poured into water and extracted into ethyl acetate (twice). The combined ethyl acetate extracts were dried through a hydrophobic frit, stripped to dryness and purified first by silica chromatography (ISCO) (40 g) eluting with 0-100% ethyl acetate:cyclohexane then 0-20% methanol:ethyl acetate and then by reverse phase chromatography (43 g, C-18) (ISCO) eluting 20-60% acetonitrile (0.05% formic acid): water (0.1% formic acid) to give the title compound as a white solid.

Workup

  1. temperatureheated for 2 hours at 50° C
  2. extractionextracted into ethyl acetate (twice)
  3. dry with materialThe combined ethyl acetate extracts were dried through a hydrophobic frit
  4. custompurified first by silica chromatography (ISCO) (40 g)
  5. washeluting with 0-100% ethyl acetate
  6. washcyclohexane then 0-20% methanol:ethyl acetate and then by reverse phase chromatography (43 g, C-18) (ISCO) eluting 20-60% acetonitrile (0.05% formic acid)

Sources & evidence

ORD record
ord-3e3b6929589b49e78d34fe62278a8efb
Source dataset
uspto-grants-2011_07
Patent number
US07977344B2

Reaction notes

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