Chloroform → 6-Amino-2-butoxy-9-{3-[(3-morpholin-4-ylpropyl)amino]propyl}-7,9-dihydro-8H-purine-8-one dimaleate

HRID 539250Notes

Reaction equation

HRID 539250 reaction equation
Cl.Cl.Cl.[NH2:4][C:5]1[N:13]=[C:12]([O:14][CH2:15][CH2:16][CH2:17][CH3:18])[N:11]=[C:10]2[C:6]=1[NH:7][C:8](=[O:32])[N:9]2[CH2:19][CH2:20][CH2:21][NH:22][CH2:23][CH2:24][CH2:25][N:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.C(=O)([O-])[O-].[Na+].[Na+].C(Cl)(Cl)Cl.[C:43]([OH:50])(=[O:49])/[CH:44]=[CH:45]\[C:46]([OH:48])=[O:47]>[Cl-].[Na+].O.CO>[C:43]([OH:50])(=[O:49])/[CH:44]=[CH:45]\[C:46]([OH:48])=[O:47].[C:43]([OH:50])(=[O:49])/[CH:44]=[CH:45]\[C:46]([OH:48])=[O:47].[NH2:4][C:5]1[N:13]=[C:12]([O:14][CH2:15][CH2:16][CH2:17][CH3:18])[N:11]=[C:10]2[C:6]=1[NH:7][C:8](=[O:32])[N:9]2[CH2:19][CH2:20][CH2:21][NH:22][CH2:23][CH2:24][CH2:25][N:26]1[CH2:27][CH2:28][O:29][CH2:30][CH2:31]1

Participants

7

Reactant 4

HCID 6212ChloroformHCID 10340Sodium CarbonateHCID 444266Maleic AcidHCID 669632426-amino-2-butoxy-9-{3-[(3-morpholin-4-ylpropyl)amino]propyl}-7,9-dihydro-8H-purine-8-one trihydrochloride

Product 1

HCID 866513626-Amino-2-butoxy-9-{3-[(3-morpholin-4-ylpropyl)amino]propyl}-7,9-dihydro-8H-purine-8-one dimaleateYield 94.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
53 °C

Procedure

To a solution of 6-amino-2-butoxy-9-{3-[(3-morpholin-4-ylpropyl)amino]propyl}-7,9-dihydro-8H-purine-8-one trihydrochloride (15.00 g, 29.02 mmol) in 10% brine (105.00 g) was added an aqueous 10% sodium carbonate to be neutralized. After adding chloroform (335.7 g), the mixture was heated to 53° C., and the aqueous layer was separated and removed. After an organic layer was concentrated, to the residue was added methanol (296.63 g) and the mixture was raised to 50° C. After methanol (59.33 g) containing maleic acid (6.74 g, 58.04 mmol) was dropped, a white crystal was confirmed. After stirring at 70° C. for 1 hour, the mixture was cooled to 5° C., a crystal was filtered, washed and dried to give the subject compound (17.60 g, 94.8%). Purity: 99.62% (HPLC)

Workup

  1. customthe aqueous layer was separated
  2. customremoved
  3. concentrationAfter an organic layer was concentrated, to the residue
  4. additionwas added methanol (296.63 g)
  5. temperaturethe mixture was raised to 50° C
  6. additionwas dropped
  7. temperaturethe mixture was cooled to 5° C.
  8. filtrationa crystal was filtered
  9. washwashed
  10. customdried

Sources & evidence

ORD record
ord-8d15dc91050643dc93b703494b74a80f
Source dataset
uspto-grants-2014_10
Patent number
US08865896B2

Reaction notes

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