Morpholine → 3-Butyl-8-chloro-1-{3-[5-(phenylmethyl)-2H-tetrazol-2-yl]propyl}-3,7-dihydro-1H-purine-2,6-dione

温度

45 °C

A mixture of 3-butyl-8-chloro-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (1.74 g, 6.1 mmol), crude 2-(3-bromopropyl)-5-(phenylmethyl)-2H-tetrazole) (1.9 g, 6.8 mmol), Cs2CO3 (2.2 g, 6.8 mmol) and DMF (60 ml) was stirred at 45° C. under nitrogen for 24 h. The mixture was degassed by applying a vacuum and then nitrogen was introduced. Pd(PPh3)4 (705 mg, 0.61 mmol) was added and the mixture degassed once more. Morpholine (5.4 ml, 61.4 mmol) was added and the mixture was stirred under nitrogen for 4 h, and then partitioned between 2M HCl (aq) and EtOAc. The organic layer was separated, washed with brine, dried (MgSO4) and concentrated, giving a yellow residue. MeOH was added and then passed down an aminopropyl column with the product eluting with 2% AcOH/MeOH. The product was further purified by the Companion™ system using EtOAc/cyclohexane mixtures. The resulting solid was stirred with boiling Et2O and filtered after cooling to rt. The title compound was collected as a white solid (1.01 g, 37%) and dried at 50° C. under vacuum.

1. customThe mixture was degassed
2. additionnitrogen was introduced
3. customthe mixture degassed once more
4. stirringthe mixture was stirred under nitrogen for 4 h
5. custompartitioned between 2M HCl (aq) and EtOAc
6. customThe organic layer was separated
7. washwashed with brine
8. dry with materialdried (MgSO4)
9. concentrationconcentrated
10. customgiving a yellow residue
11. washeluting with 2% AcOH/MeOH
12. customThe product was further purified by the Companion™ system
13. stirringThe resulting solid was stirred with boiling Et2O
14. filtrationfiltered
15. temperatureafter cooling to rt
16. customThe title compound was collected as a white solid (1.01 g, 37%)
17. customdried at 50° C. under vacuum

ORDレコード

ord-b8ebdefdd3be49389922a1f66c11371c

出典データセット

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08143264B2