1,3-Dibromopropane → 9-[3-(1-Azetidinyl)propyl]-2-(butyloxy)-8-(methyloxy)-9H-purin-6-amine

Temperature

50 °C

2-(Butyloxy)-8-(methyloxy)-1H-purin-6-amine trifluoroacetate (100 mg, 0.285 mmol) was dissolved in DMF (1 ml) and potassium carbonate (98 mg, 0.712 mmol) was added. The reaction mixture was stirred at 50° C. under nitrogen for 1 hour and then cooled to room temperature. 1,3-Dibromopropane (0.029 ml, 0.285 mmol) was added and after stirring for a further 40 mins. azetidine (0.038 ml, 0.569 mmol) and triethylamine (0.079 ml, 0.569 mmol) in DMF (1 ml) were added. The reaction mixture was then stirred for a further 18 hours. The solvent was removed and the residue was partitioned between dichloromethane (2 ml) and water (2 ml). The layers were separated using a hydrophobic frit and the aqueous phase was re-extracted with DCM (2 ml). The combined organic extracts were concentrated and the residue was dissolved in 1:1 MeOH:DMSO (1 ml) and purified by MDAP (Method A). The product containing fractions were evaporated under a stream of nitrogen to give the title compound as a white solid (13 mg).

1. temperaturecooled to room temperature
2. stirringafter stirring for a further 40 mins
3. stirringThe reaction mixture was then stirred for a further 18 hours
4. customThe solvent was removed
5. customthe residue was partitioned between dichloromethane (2 ml) and water (2 ml)
6. customThe layers were separated
7. extractionthe aqueous phase was re-extracted with DCM (2 ml)
8. concentrationThe combined organic extracts were concentrated
9. dissolutionthe residue was dissolved in 1:1 MeOH
10. customDMSO (1 ml) and purified by MDAP (Method A)
11. additionThe product containing fractions
12. customwere evaporated under a stream of nitrogen

ORD record

ord-cf1a6f57eedc4635992f7512389232a3

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09233962B2