Potassium Carbonate → 3-Bromopentane

HRID 2403909Notes

Reaction equation

HRID 2403909 reaction equation
[CH2:1]([O:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([O:23]C)[N:12]2[CH2:15][CH2:16][CH:17]2[CH2:22][CH2:21][CH2:20][NH:19][CH2:18]2)=[C:8]([NH2:25])[N:7]=1)[CH2:2][CH2:3][CH3:4].CCN(C(C)C)C(C)C.C(=O)([O-])[O-].[K+].[K+].[Br:41][CH:42]([CH2:45][CH3:46])[CH2:43][CH3:44]>C(#N)C.CN(C=O)C.CO.CS(C)=O>[Br:41][CH:42]([CH2:45][CH3:46])[CH2:43][CH3:44].[NH2:25][C:8]1[N:7]=[C:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])[N:14]=[C:13]2[C:9]=1[NH:10][C:11](=[O:23])[N:12]2[CH2:15][CH2:16][CH:17]1[CH2:22][CH2:21][CH2:20][N:19]([CH:42]([CH2:45][CH3:46])[CH2:43][CH3:44])[CH2:18]1

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 157383-BromopentaneHCID 81531Diisopropylethylamine2×HCID 583062622-(Butyloxy)-8-(methyloxy)-9-[2-(3-piperidinyl)ethyl]-9H-purin-6-amine

Product 2

HCID 157383-BromopentaneHCID 672333456-Amino-2-(butyloxy)-9-{2-[1-(1-ethylpropyl)-3-piperidinyl]ethyl}-7,9-dihydro-8H-purin-8-one

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
50 °C

Procedure

A solution of 3-bromopentane was prepared by dissolving 1 mmole in acetonitrile (1 ml). A portion of this solution (0.12 ml, equivalent to 0.12 mmol) was added to a test tube. 2-(Butyloxy)-8-(methyloxy)-9-[2-(3-piperidinyl)ethyl]-9H-purin-6-amine (435 mg, 1.2 mmol) was dissolved in DMF (6.0 ml) and an aliquot (0.5 ml, 0.1 mmol) dispensed to the tube. DIPEA (40 μL, 0.23 mmol) and potassium carbonate (46 mg, 0.3 mmol) added, and heated to 50° C. for 18 hr. An additional aliquot of 3-bromopentane in acetonitrile (80 uL, 0.08 mmol) (total added 0.2 mmol) and DIPEA (40 uL, 0.23 mmol) was added and continued stirring with heat at 50° C. for a further 18 hours. DMSO:MeOH (200 uL) was added, the mixture filtered and purified by Mass Directed AutoPrep (Method A). The solvent was evaporated in vacuo using the Genevac. The residue was redissolved in a solution of 4M HCl/dioxane (0.2 ml) and allowed to stand at room temperature for 4 hours. The solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus. The material was redissolved in methanol (0.5 ml) and applied to an aminopropyl SPE (0.1 g, 3 ml, preconditioned in methanol (1.5 ml)). The product was eluted with additional methanol (1.5 ml). The solvent was removed to give the title compound (6 mg).

Workup

  1. additionA portion of this solution (0.12 ml, equivalent to 0.12 mmol) was added to a test tube
  2. temperaturewith heat at 50° C. for a further 18 hours
  3. filtrationthe mixture filtered
  4. custompurified by Mass Directed AutoPrep (Method A)
  5. customThe solvent was evaporated in vacuo
  6. dissolutionThe residue was redissolved in a solution of 4M HCl/dioxane (0.2 ml)
  7. customThe solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus
  8. dissolutionThe material was redissolved in methanol (0.5 ml)
  9. washThe product was eluted with additional methanol (1.5 ml)
  10. customThe solvent was removed

Sources & evidence

ORD record
ord-8d9be9b149b143fab21f4c31f508b6f6
Source dataset
uspto-grants-2014_08
Patent number
US08802684B2

Reaction notes

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