2-Bromoethanol → HCID 53355058, compound

HRID 2038187Notes

Reaction equation

HRID 2038187 reaction equation
[CH2:1]([O:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([O:25]C)[N:12]2[CH2:15][CH2:16][CH2:17][CH2:18][CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)=[C:8]([NH2:27])[N:7]=1)[CH2:2][CH2:3][CH3:4].Br[CH2:29][CH2:30][OH:31].CCN(C(C)C)C(C)C>CN(C=O)C.CS(C)=O>[NH2:27][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:25])[N:12]2[CH2:15][CH2:16][CH2:17][CH2:18][CH:19]1[CH2:20][CH2:21][N:22]([CH2:29][CH2:30][OH:31])[CH2:23][CH2:24]1

Participants

6

Reactant 3

HCID 108982-Bromoethanol2×HCID 81531Diisopropylethylamine2×HCID 583062222-(Butyloxy)-8-(methyloxy)-9-[4-(4-piperidinyl)butyl]-9H-purin-6-amine2×

Product 1

HCID 53355058HCID 53355058, compoundYield 32.7%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

2-(Butyloxy)-8-(methyloxy)-9-[4-(4-piperidinyl)butyl]-9H-purin-6-amine (for example, as prepared for Intermediate 34) (0.038 g, 0.10 mmol) in DMF (0.4 mL) was added to 2-bromoethanol (0.0085 mL, 0.12 mmol). DIPEA (0.040 mL, 0.23 mmol) was added and the reaction mixture heated at 50° C. for 18 hours. An additional aliquot of the 2-bromoethanol (commercially available, for example, from Aldrich) (0.015 mL) and DIPEA (0.040 mL, 0.23 mmol) were added and heating continued for a further 7 hours. The reaction mixture were stirred at room temperature for 72 hours then diluted with DMSO:MeOH (0.2 mL) and the resultant solution purified by MDAP (Method A). Appropriate fractions were combined and evaporated in vacuo. The residue was dissolved in 4M HCl in dioxane (0.2 mL) and allowed to stand at room temperature for 18 hours. The solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus. The samples were dissolved in 1:1 MeOH:DMSO (0.6 mL) and purified by Mass Directed AutoPrep on Sunfire C18 column using Acetonitrile Water with a TFA modifier. The solvent was evaporated in vacuo. The residue 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 washed with methanol (1.5 mL). The solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus to give the title compound (0.0133 g).

Workup

  1. temperatureheating
  2. customMeOH (0.2 mL) and the resultant solution purified by MDAP (Method A)
  3. customevaporated in vacuo
  4. dissolutionThe residue was dissolved in 4M HCl in dioxane (0.2 mL)
  5. waitto stand at room temperature for 18 hours
  6. customThe solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus
  7. dissolutionThe samples were dissolved in 1:1 MeOH
  8. customDMSO (0.6 mL) and purified by Mass Directed AutoPrep on Sunfire C18 column
  9. customThe solvent was evaporated in vacuo
  10. dissolutionThe residue was redissolved in methanol (0.5 mL)
  11. washThe cartridge was washed with methanol (1.5 mL)
  12. customThe solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus

Sources & evidence

ORD record
ord-616f03b51264453aa8fba3ed7b953a30
Source dataset
uspto-grants-2013_11
Patent number
US08575340B2

Reaction notes

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