Potassium Carbonate → 2-[(2-Cyclopropylethyl)oxy]-8-(methoxy)-9-(tetrahydro-3-furanylmethyl)-9H-purin-6-amine

HRID 1011059Notes

Reaction equation

HRID 1011059 reaction equation
FC(F)(F)C(O)=O.[CH:8]1([CH2:11][CH2:12][O:13][C:14]2[NH:15][C:16]([NH2:25])=[C:17]3[C:21]([N:22]=2)=[N:20][C:19]([O:23][CH3:24])=[N:18]3)[CH2:10][CH2:9]1.C(=O)([O-])[O-].[K+].[K+].CS(O[CH2:37][CH:38]1[CH2:42][CH2:41][O:40][CH2:39]1)(=O)=O.ClC1N=C2C(N=CN2CC2CCOCC2)=C(Cl)N=1>CN(C)C=O.C(OCC)(=O)C>[CH:8]1([CH2:11][CH2:12][O:13][C:14]2[N:22]=[C:21]3[C:17]([N:18]=[C:19]([O:23][CH3:24])[N:20]3[CH2:37][CH:38]3[CH2:42][CH2:41][O:40][CH2:39]3)=[C:16]([NH2:25])[N:15]=2)[CH2:10][CH2:9]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 22273010(Tetrahydrofuran-3-yl)methyl methanesulfonateHCID 576997032,6-Dichloro-9-(tetrahydro-2H-pyran-4-ylmethyl)-9H-purineHCID 178494009HCID 178494009, compound

Product 1

HCID 576996582-[(2-Cyclopropylethyl)oxy]-8-(methoxy)-9-(tetrahydro-3-furanylmethyl)-9H-purin-6-amine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-[(2-cyclopropylethyl)oxy]-8-(methoxy)-1H-purin-6-amine trifluoroacetic acid salt (2.89 g) in dry N,N-dimethylformamide (32 ml) under nitrogen and at room temperature, was added potassium carbonate (4.41 g) in one go. The reaction was heated to 60° C. and stirred for 90 minutes. A solution of tetrahydro-3-furanylmethyl methanesulfonate, Isomer 2 (1.869 g) in dry DMF (3 ml) was then added gradually via pipette. The reaction was heated to 70° C. and left to stir overnight. Still 22% starting material present by LCMS, therefore increased temperature to 90° C. and stirred for a further 3 hours at this temperature. The reaction was cooled and diluted with ethyl acetate (100 ml) and washed with water (50 ml) and brine (50 ml). The organic layer was concentrated in vacuo to yield an orange oil. The product was purified by C18 reverse phase chromatography using water (0.1% formic acid)-acetonitrile (0.05% formic acid) as eluant (10-60%) to afford the title compound as an orange viscous oil (1.45 g).

Workup

  1. temperatureThe reaction was heated to 70° C.
  2. waitleft
  3. stirringto stir overnight
  4. temperatureincreased temperature to 90° C.
  5. stirringstirred for a further 3 hours at this temperature
  6. temperatureThe reaction was cooled
  7. washwashed with water (50 ml) and brine (50 ml)
  8. concentrationThe organic layer was concentrated in vacuo
  9. customto yield an orange oil
  10. customThe product was purified by C18 reverse phase chromatography

Sources & evidence

ORD record
ord-2d8d1935695d4250bc0ecc620c7eaee5
Source dataset
uspto-grants-2011_07
Patent number
US07977344B2

Reaction notes

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