Morpholine → 8-Chloro-1-{4-[2-oxo-1-(phenylmethyl)-3-pyrrolidinyl]butyl}-3-pentyl-3,7-dihydro-1H-purine-2,6-dione

HRID 1097727

Reaktionsgleichung

Reaktionsgleichung von HRID 1097727
[Cl:1][C:2]1[N:10](CC=C)[C:9]2[C:8](=[O:14])[NH:7][C:6](=[O:15])[N:5]([CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:4]=2[N:3]=1.Br[CH2:22][CH2:23][CH2:24][CH2:25][CH:26]1[CH2:30][CH2:29][N:28]([CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:27]1=[O:38].C(=O)([O-])[O-].[K+].[K+].N1CCOCC1>C1COCC1.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>[Cl:1][C:2]1[NH:10][C:9]2[C:8](=[O:14])[N:7]([CH2:22][CH2:23][CH2:24][CH2:25][CH:26]3[CH2:30][CH2:29][N:28]([CH2:31][C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)[C:27]3=[O:38])[C:6](=[O:15])[N:5]([CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:4]=2[N:3]=1

Komponenten

7

Edukt 4

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 592995577-Allyl-8-chloro-3-pentyl-1H-purine-2,6(3H,7H)-dioneHCID 593958573-(4-Bromobutyl)-1-(phenylmethyl)-2-pyrrolidinone

Produkt 1

HCID 593958558-Chloro-1-{4-[2-oxo-1-(phenylmethyl)-3-pyrrolidinyl]butyl}-3-pentyl-3,7-dihydro-1H-purine-2,6-dione

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a solution of 8-chloro-3-pentyl-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (0.086 g, 0.29 mmol) and 3-(4-bromobutyl)-1-(phenylmethyl)-2-pyrrolidinone (0.17 g, 0.55 mmol, 1:1 mixture with 2-(phenylmethyl)-2-azaspiro[4.4]nonan-1-one) in THF (5 ml) was added potassium carbonate (0.08 g, 0.58 mmol) and the mixture heated and stirred at 50° C. for 18 h. The solution was allowed to cool then degassed (sequential evacuation followed by addition of nitrogen×3) and Pd(PPh3)4 (0.09 g, 0.077 mmol) followed by morpholine (0.2 ml, 2.2 mmol) added and the solution stirred at ambient temperature for 18 h. The solution was separated between ethyl acetate and dil HCl and the organics washed with brine, dried and concentrated. Purification of the residues using an aminopropyl SPE (5 g) eluting first with MeOH then 5% AcOH/MeOH yielded the title compound as a yellow oil which crystallised on standing under ether (0.031 g, 22%).

Aufarbeitung

  1. temperaturethe mixture heated
  2. temperatureto cool
  3. customthen degassed
  4. additionadded
  5. stirringthe solution stirred at ambient temperature for 18 h
  6. customThe solution was separated between ethyl acetate and dil HCl
  7. washthe organics washed with brine
  8. customdried
  9. concentrationconcentrated
  10. customPurification of the residues
  11. washeluting first with MeOH

Quellen und Nachweise

ORD-Eintrag
ord-575039136bbd40398a94ce0be4c619b7
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143264B2

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