Trifluoroacetic acid → 2,6-Bis-((R)-3-methyl-morpholin-4-yl)-9-(tetrahydro-pyran-2-yl)-9H-purine

HRID 522803Notes

Reaction equation

HRID 522803 reaction equation
[CH3:1][C@@H:2]1[CH2:7][O:6][CH2:5][CH2:4][N:3]1[C:8]1[N:16]=[C:15]2[C:11]([N:12]=[CH:13][NH:14]2)=[C:10]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][C@H:18]2[CH3:23])[N:9]=1.[O:24]1[CH:29]=[CH:28][CH2:27][CH2:26][CH2:25]1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.FC(F)(F)C(O)=O.C([O-])([O-])=O.[Na+].[Na+]>CCOC(C)=O>[CH3:1][C@@H:2]1[CH2:7][O:6][CH2:5][CH2:4][N:3]1[C:8]1[N:16]=[C:15]2[C:11]([N:12]=[CH:13][N:14]2[CH:25]2[CH2:26][CH2:27][CH2:28][CH2:29][O:24]2)=[C:10]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][C@H:18]2[CH3:23])[N:9]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 80803,4-dihydro-2H-pyran2×HCID 9845Trifluoroacetic anhydrideHCID 10340Sodium CarbonateHCID 178461598HCID 178461598, compound

Product 1

HCID 895255782,6-Bis-((R)-3-methyl-morpholin-4-yl)-9-(tetrahydro-pyran-2-yl)-9H-purineYield 79%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
70 °C

Procedure

2,6-Bis-((R)-3-methyl-morpholin-4-yl)-9H-purine (600 mg, 1.89 mmol) was dissolved in EtOAc (25 mL) under argon. After addition of 3,4-dihydro-2H-pyrane (172 μl, 1.89 mmol), trifluoro acetic acid anhydride (27 μl, 188 μmol), and trifluoro acetic acid (319 μl, 4.15 mmol), the reaction mixture was heated to 70° C. After 6 hours, 3,4-dihydro-2H-pyrane (1.44 mL, 15.7 mmol) was added. The reaction was then stirred for 22 hours at 70° C. and then cooled to room temperature. 500 mg of solid Na2CO3 was added and stirring continued for 10 minutes. The reaction mixture was diluted with EtOAc, the organic layer was separated, dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue, which was purified by column chromatography (40 g SiO2, heptane/EtOAc in a gradient from 9/1 to 2/3) to give the product as a foam (600 mg, 79%).

Workup

  1. temperaturecooled to room temperature
  2. stirringstirring
  3. waitcontinued for 10 minutes
  4. customthe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give a residue, which
  9. customwas purified by column chromatography (40 g SiO2, heptane/EtOAc in a gradient from 9/1 to 2/3)

Sources & evidence

ORD record
ord-53e2375d96e14881bb07946ca8ef14bd
Source dataset
uspto-grants-2016_05
Patent number
US09334271B2

Reaction notes

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