N-(3-Aminopropyl)morpholine → 6-amino-2-butoxy-9-{3-[(3-morpholin-4-ylpropyl)amino]propyl}-7,9-dihydro-8H-purine-8-one trihydrochloride

HRID 539249Notes

Reaction equation

HRID 539249 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.CS(O[CH2:16][CH2:17][CH2:18][N:19]1[C:27]([O:28]C)=[N:26][C:25]2[C:20]1=[N:21][C:22]([O:31][CH2:32][CH2:33][CH2:34][CH3:35])=[N:23][C:24]=2[NH2:30])(=O)=O.[Cl-:36].[Na+].O>>[ClH:36].[ClH:36].[ClH:36].[NH2:30][C:24]1[N:23]=[C:22]([O:31][CH2:32][CH2:33][CH2:34][CH3:35])[N:21]=[C:20]2[C:25]=1[NH:26][C:27](=[O:28])[N:19]2[CH2:18][CH2:17][CH2:16][NH:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1

Participants

4

Reactant 3

HCID 61055N-(3-Aminopropyl)morpholineHCID 57417360Sodium chloride; waterHCID 581596253-(6-Amino-2-butoxy-8-methoxy-9H-purin-9-yl)propyl methanesulfonate

Product 1

HCID 669632426-amino-2-butoxy-9-{3-[(3-morpholin-4-ylpropyl)amino]propyl}-7,9-dihydro-8H-purine-8-one trihydrochloride

Conditions

Temperature
28 °C

Procedure

To N-(3-aminopropyl)morpholine (86.90 g, 602.52 mmol) which was cooled to 3° C. was in several times added 3-(6-amino-2-butoxy-8-methoxy-9H-purin-9-yl)propyl methanesulfonate (amount corresponding to dried weight 15.00 g (40.17 mmol)) not to exceed to 20° C. After stirring at 28° C. for 10 hours, thereto was added 15% brine (160.00 g), and the mixture was extracted with a mixture of toluene (194.08 g) and THF (199.8 g). After removal of the organic solvent, concentrated hydrochloric acid (41.84 g) was added thereto, and the mixture was stirred at 25° C. for 3 hours. After removal by distillation of the solvent, to the residue was added methanol (118.65 g), followed by raising to 55° C. Isopropanol (353.25 g) was dropped thereto and the mixture was crystallized and further raised to 70° C. After one hour, the mixture was cooled to 20° C. The resulting crystal was filtered, washed and dried to give the subject compound (16.80 g, 77.5% by 2 steps). Purity: 99.70% (HPLC)

Workup

  1. customto exceed to 20° C
  2. extractionthe mixture was extracted with a mixture of toluene (194.08 g) and THF (199.8 g)
  3. customAfter removal of the organic solvent, concentrated hydrochloric acid (41.84 g)
  4. additionwas added
  5. stirringthe mixture was stirred at 25° C. for 3 hours
  6. customAfter removal
  7. distillationby distillation of the solvent
  8. additionto the residue was added methanol (118.65 g)
  9. temperatureby raising to 55° C
  10. additionIsopropanol (353.25 g) was dropped
  11. customthe mixture was crystallized
  12. temperaturefurther raised to 70° C
  13. waitAfter one hour
  14. temperaturethe mixture was cooled to 20° C
  15. filtrationThe resulting crystal was filtered
  16. washwashed
  17. customdried
  18. customto give the subject compound (16.80 g, 77.5% by 2 steps)

Sources & evidence

ORD record
ord-c664be475ac24cf7b6548960f30a8ec3
Source dataset
uspto-grants-2014_10
Patent number
US08865896B2

Reaction notes

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