Dimethyl Sulfoxide → 6-Amino-2-(butyloxy)-9-[2-(1-propyl-4-piperidinyl)ethyl]-7,9-dihydro-8H-purin-8-one

HRID 1044996Notes

Reaction equation

HRID 1044996 reaction equation
I[CH2:2][CH2:3][CH3:4].[CH2:5]([O:9][C:10]1[N:18]=[C:17]2[C:13]([N:14]=[C:15]([O:27]C)[N:16]2[CH2:19][CH2:20][CH:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)=[C:12]([NH2:29])[N:11]=1)[CH2:6][CH2:7][CH3:8].CCN(C(C)C)C(C)C.CS(C)=O>CN(C=O)C>[NH2:29][C:12]1[N:11]=[C:10]([O:9][CH2:5][CH2:6][CH2:7][CH3:8])[N:18]=[C:17]2[C:13]=1[NH:14][C:15](=[O:27])[N:16]2[CH2:19][CH2:20][CH:21]1[CH2:26][CH2:25][N:24]([CH2:2][CH2:3][CH3:4])[CH2:23][CH2:22]1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 336431-Iodopropane2×HCID 81531Diisopropylethylamine2×HCID 583062442-(Butyloxy)-8-(methyloxy)-9-[2-(4-piperidinyl)ethyl]-9H-purin-6-amine

Product 1

HCID 671817436-Amino-2-(butyloxy)-9-[2-(1-propyl-4-piperidinyl)ethyl]-7,9-dihydro-8H-purin-8-oneYield 13.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

1-Iodopropane (0.1 mmol) was weighed into a vial and an aliquot (0.4 ml, 0.12 mmol) of a solution of 2-(butyloxy)-8-(methyloxy)-9-[2-(4-piperidinyl)ethyl]-9H-purin-6-amine (0.418 g mg, 1.2 mmol) suspended in DMF (4.8 ml) was added to each tube. DIPEA (40 μl, 0.229 mmol) was added finally to each tube, the tube was heated at 50° C. for 18 hours. An additional portion of 1-iodopropane (15 μl) and DIPEA (20 μl) was added to each tube and heating continued for a further 18 hours. DMSO (200 uL) was added and the solution and the mixture purified by Mass Directed AutoPrep (Method A). The solvent was evaporated in vacuo using the Genevac. The residue was redissolved in 4M HCl/dioxane (0.2 ml), capped and stood at room temperature for 18 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 top of 0.1 g aminopropyl SPE (preconditioned with methanol, 1.5 ml). The cartridge was eluted with methanol (1.5 ml) and the solvent was removed to give the title compound (5.1 mg).

Workup

  1. additionwas added to each tube
  2. temperatureheating
  3. customthe solution and the mixture purified by Mass Directed AutoPrep (Method A)
  4. customThe solvent was evaporated in vacuo
  5. dissolutionThe residue was redissolved in 4M HCl/dioxane (0.2 ml)
  6. customcapped
  7. waitstood at room temperature for 18 hours
  8. customThe solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus
  9. dissolutionThe material was redissolved in methanol (0.5 ml)
  10. washThe cartridge was eluted with methanol (1.5 ml)
  11. customthe solvent was removed

Sources & evidence

ORD record
ord-af5182e3c8ef4687a6565bc6fbdad69d
Source dataset
uspto-grants-2013_10
Patent number
US08563717B2

Reaction notes

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