Morpholine → 8-Chloro-1-(3-{1-[(2-chloro-6-fluorophenyl)methyl]-1H-pyrazol-4-yl}propyl)-3-pentyl-3,7-dihydro-1H-purine-2,6-dione

HRID 1097633Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1097633
[Cl:1][C:2]1[N:10](CC=C)[C:9]2[C:8](=[O:14])[N:7]([CH2:15][CH2:16][CH2:17][C:18]3[CH:19]=[N:20][NH:21][CH:22]=3)[C:6](=[O:23])[N:5]([CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[C:4]=2[N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl:35][C:36]1[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[C:37]=1[CH2:38]Br.N1CCOCC1>CN(C=O)C.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]([CH2:15][CH2:16][CH2:17][C:18]3[CH:22]=[N:21][N:20]([CH2:38][C:37]4[C:40]([F:44])=[CH:41][CH:42]=[CH:43][C:36]=4[Cl:35])[CH:19]=3)[C:6](=[O:23])[N:5]([CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[C:4]=2[N:3]=1

Komponenten

7

Edukt 4

HCID 8083MorpholineHCID 10340Sodium CarbonateHCID 27736252-Chloro-6-fluorobenzyl bromideHCID 593958038-Chloro-3-pentyl-7-(2-propen-1-yl)-1-[3-(1H-pyrazol-4-yl)propyl]-3,7-dihydro-1H-purine-2,6-dione

Produkt 1

HCID 159458498-Chloro-1-(3-{1-[(2-chloro-6-fluorophenyl)methyl]-1H-pyrazol-4-yl}propyl)-3-pentyl-3,7-dihydro-1H-purine-2,6-dioneAusbeute 74,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
45 °C

Versuchsvorschrift

8-Chloro-3-pentyl-7-(2-propen-1-yl)-1-[3-(1H-pyrazol-4-yl)propyl]-3,7-dihydro-1H-purine-2,6-dione (61 mg, 0.15 mmol) in dry DMF (2 ml) was stirred with sodium carbonate (64 mg, 0.6 mmol) and 2-chloro-6-fluorobenzyl bromide (134 mg, 0.6 mmol) and heated at 45° C. for 18 h under nitrogen. After cooling to rt the mixture was degassed by evacuating and readmitting nitrogen, and stirred with tetrakis(triphenylphosphine)palladium(0) (35 mg, 0.303 mmol) and morpholine (0.13 ml) for 5.5 h. The mixture was partitioned between EtOAc and 2M HCl, the organic phase separated and evaporated and the residue purified by aminopropyl SPE (5 g, washing with THF-MeOH (1:1) then neat MeOH and finally eluting with DCM-MeOH (1:1) containing 5% AcOH) to give the title compound (57 mg) as a solid.

Aufarbeitung

  1. temperatureAfter cooling to rt the mixture
  2. customwas degassed
  3. customby evacuating
  4. customThe mixture was partitioned between EtOAc and 2M HCl
  5. customthe organic phase separated
  6. customevaporated
  7. customthe residue purified by aminopropyl SPE (5 g
  8. washwashing with THF-MeOH (1:1)
  9. washneat MeOH and finally eluting with DCM-MeOH (1:1)
  10. additioncontaining 5% AcOH)

Quellen und Nachweise

ORD-Eintrag
ord-c1a807c76b824a328e3ab906ef5a1fbd
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143264B2

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