1-(2-Hydroxyethyl)piperazine → HCID 53355166, compound

Temperature

50 °C

2-(Butyloxy)-9-(4-chlorobutyl)-8-(methyloxy)-9H-purin-6-amine (for example, as prepared for Intermediate 42) (100 mg, 0.305 mmol), DIPEA (0.160 mL, 0.915 mmol) and 2-(1-piperazinyl)ethanol (commercially available, for example, from Aldrich) (0.075 mL, 0.61 mmol) were dissolved in DMF (2.2 mL). The reaction mixture was stirred and heated at 50° C. under nitrogen overnight. Additional 2-(1-piperazinyl)ethanol (0.075 mL, 0.61 mmol) was added and the mixture heated at 80° C. for 20 hours. The reaction mixture was cooled down to room temp and partitioned between water (5 mL) and DCM (6 mL). The layers were separated using a hydrophobic frit and the aqueous washed with DCM (5 mL). The combined organics were concentrated under vacuum. The residues were dissolved in DMSO (1 mL) and purified by MDAP on Xbridge column using Acetonitrile Water with an ammonium carbonate modifier. The desired fractions were combined and concentrated under nitrogen blowdown. The residue was dissolved in methanol (2 mL) and HCl 4M in dioxane (3 mL) was added. The reaction mixture was stirred for 30 mins and then left in solution at room temp for 1 hour. The reaction mixture was concentrated under nitrogen blowdown and then dissolved in MeOH and eluted through an NH2 (1 g). The columns were washed with MeOH (3 CV). The solvent was removed under nitrogen blowdown to give a brown solid. The samples were dissolved in DMSO (1 mL) and purified by MDAP on Xbridge column using Acetonitrile Water with an ammonium carbonate modifier. The desired fractions were combined and concentrated under nitrogen blowdown to give the title compound as a white solid (0.0262 g).

1. temperaturethe mixture heated at 80° C. for 20 hours
2. temperatureThe reaction mixture was cooled down to room temp
3. custompartitioned between water (5 mL) and DCM (6 mL)
4. customThe layers were separated
5. washthe aqueous washed with DCM (5 mL)
6. concentrationThe combined organics were concentrated under vacuum
7. dissolutionThe residues were dissolved in DMSO (1 mL)
8. custompurified by MDAP on Xbridge column
9. concentrationconcentrated under nitrogen
10. dissolutionThe residue was dissolved in methanol (2 mL)
11. additionHCl 4M in dioxane (3 mL) was added
12. stirringThe reaction mixture was stirred for 30 mins
13. concentrationThe reaction mixture was concentrated under nitrogen blowdown
14. dissolutiondissolved in MeOH
15. washeluted through an NH2 (1 g)
16. washThe columns were washed with MeOH (3 CV)
17. customThe solvent was removed under nitrogen
18. customto give a brown solid
19. custompurified by MDAP on Xbridge column
20. concentrationconcentrated under nitrogen

ORD record

ord-c29da18686a64d26bc7177e712ded268

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08575340B2