Bromide ion → 2-Butoxy-9-(1-tert-butoxycarbonylpiperidin-4-ylmethyl)-8-methoxyadenine

HRID 1044852Notes

Reaction equation

HRID 1044852 reaction equation
C(=O)([O-])[O-].[K+].[K+].FC(F)(F)C(O)=O.[CH2:14]([O:18][C:19]1[N:27]=[C:26]2[C:22]([N:23]=[C:24]([O:28][CH3:29])[NH:25]2)=[C:21]([NH2:30])[N:20]=1)[CH2:15][CH2:16][CH3:17].Br[CH2:32][CH:33]1[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]1.[Br-]>CN(C)C=O.O>[NH2:30][C:21]1[N:20]=[C:19]([O:18][CH2:14][CH2:15][CH2:16][CH3:17])[N:27]=[C:26]2[C:22]=1[N:23]=[C:24]([O:28][CH3:29])[N:25]2[CH2:32][CH:33]1[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:43])([CH3:45])[CH3:44])=[O:40])[CH2:35][CH2:34]1

Participants

7

Reactant 4

HCID 259Bromide ionHCID 11430Potassium CarbonateHCID 15512811tert-Butyl 4-(bromomethyl)piperidine-1-carboxylateHCID 178450370HCID 178450370, compound

Product 1

HCID 583060912-Butoxy-9-(1-tert-butoxycarbonylpiperidin-4-ylmethyl)-8-methoxyadenineYield 94.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

Potassium carbonate (650 mg) was added to a solution of 2-butoxy-8-methoxy-9H-purin-6-amine trifluoroacetate salt (550 mg) in dry N,N-dimethylformamide (5.5 ml) and the reaction mixture heated at 60° C. for 1 hour. 1,1-Dimethylethyl 4-(bromomethyl)-1-piperidinecarboxylate (500 mg) was added using additional DMF (1.5 ml) to transfer the residual bromide and the reaction mixture stirred at 50° C. for 3 hours. After 16 hours at room temperature, heating at 50° C. was continued for another 5 hours to complete the reaction. Water was added and the reaction mixture extracted three times with ethyl acetate. The combined organic extracts were washed with water, dried over anhydrous sodium sulfate, filtered, concentrated and dried under high vacuum. Purification by chromatography on silica gel eluting with a gradient of 1-2.5% methanol in chloroform afforded the title compound as yellow solid (640 mg).

Workup

  1. waitAfter 16 hours at room temperature
  2. temperatureheating at 50° C.
  3. waitwas continued for another 5 hours
  4. customthe reaction
  5. extractionthe reaction mixture extracted three times with ethyl acetate
  6. washThe combined organic extracts were washed with water
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customdried under high vacuum
  11. customPurification by chromatography on silica gel eluting with a gradient of 1-2.5% methanol in chloroform

Sources & evidence

ORD record
ord-ac9a907958654812ba0058cf65645e90
Source dataset
uspto-grants-2013_10
Patent number
US08563717B2

Reaction notes

Loading…