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

HRID 1097644Notes

Reaction equation

HRID 1097644 reaction equation
[CH2:1]([N:5]1[C:13]2[N:12]=[C:11]([Cl:14])[N:10](CC=C)[C:9]=2[C:8](=[O:18])[NH:7][C:6]1=[O:19])[CH2:2][CH2:3][CH3:4].Br[CH2:21][CH2:22][CH2:23][N:24]1[N:28]=[N:27][C:26]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[N:25]1.C([O-])([O-])=O.[Cs+].[Cs+].N1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO.CN(C=O)C>[CH2:1]([N:5]1[C:13]2[N:12]=[C:11]([Cl:14])[NH:10][C:9]=2[C:8](=[O:18])[N:7]([CH2:21][CH2:22][CH2:23][N:24]2[N:28]=[N:27][C:26]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[N:25]2)[C:6]1=[O:19])[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 592995823-butyl-8-chloro-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dioneHCID 668128382-(3-bromopropyl)-5-(phenylmethyl)-2H-tetrazole

Product 1

HCID 593954183-Butyl-8-chloro-1-{3-[5-(phenylmethyl)-2H-tetrazol-2-yl]propyl}-3,7-dihydro-1H-purine-2,6-dione

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-b8ebdefdd3be49389922a1f66c11371c
Source dataset
uspto-grants-2012_03
Patent number
US08143264B2

Reaction notes

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