Triethylamine → 5-Butyl-3-(5-chloropent-1-yn-1-yl)-N-(2,4-dimethoxybenzyl)-1H-Pyrazolo[4,3-d]pyrimidin-7-amine

HRID 705128Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 705128
C(N(CC)CC)C.[CH2:8]([C:12]1[N:13]=[C:14]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:25]=2[O:32][CH3:33])[C:15]2[NH:20][N:19]=[C:18](I)[C:16]=2[N:17]=1)[CH2:9][CH2:10][CH3:11].[Cl:34][CH2:35][CH2:36][CH2:37][C:38]#[CH:39]>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu](I)I>[CH2:8]([C:12]1[N:13]=[C:14]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:25]=2[O:32][CH3:33])[C:15]2[NH:20][N:19]=[C:18]([C:39]#[C:38][CH2:37][CH2:36][CH2:35][Cl:34])[C:16]=2[N:17]=1)[CH2:9][CH2:10][CH3:11]

Komponenten

7

Edukt 3

HCID 8471TriethylamineHCID 843081-Pentyne, 5-chloro-2×HCID 178441817HCID 178441817, Verbindung

Produkt 1

HCID 1784418105-Butyl-3-(5-chloropent-1-yn-1-yl)-N-(2,4-dimethoxybenzyl)-1H-Pyrazolo[4,3-d]pyrimidin-7-amineAusbeute 155,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 83717Copper iodideKatalysatorHCID 6102075Dichlorobis(triphenylphosphine)palladiumKatalysatorHCID 6228DimethylformamideLösungsmittel3×

Versuchsvorschrift

Bis(triphenylphosphine)palladium(II)dichloride (101 mg, 0.144 mmol), triethylamine (0.403 mL, 2.89 mmol) and copper iodide (55.0 mg, 0.289 mmol) were added to a nitogen degassed solution of 5-butyl-N-(2,4-dimethoxybenzyl)-3-iodo-1H-pyrazolo[4,3-d]pyrimidin-7-amine (900 mg, 1.926 mmol) in anhydrous N,N-dimethylformamide (23 mL). The mixture was stirred under a nitrogen atmosphere and heated to 60° C. before the addition of 5-chloropent-1-yne (296 mg, 2.89 mmol) in anhydrous N,N-dimethylformamide (2 mL). The reaction was stirred at 60° C. for 3 hours. A further 0.30 equivalents of 5-chloropent-1-yne (59 mg, 0.575 mmol) in anhydrous N,N-dimethylformamide (1 mL) was added to the reaction. The mixture was stirred at 60° C. for a further 2.5 hours and then allowed to cool to room temperature overnight. The reaction mixture was evaporated in-vacuo to yield a brown oil. The resulting oil was partitioned between ethyl acetate (25 mL) and water/brine (1:1, 10 mL). The organic layer was separated, passed through a hydrophobic frit and evaporated in-vacuo to yield a brown oil (1.32 g). The oil was dissolved in the minimum volume of dichloromethane, loaded onto a 100 g silica cartridge and purified by chromatography using a 0-100% ethyl acetate in cyclohexane gradient over 60 minutes. Appropriate fractions were combined and evaporated in-vacuo to yield an orange oil. The oil was dissolved in the minimum volume of dichloromethane, loaded onto a 100 g silica cartridge and re-purified by chromatography using a 0-100% ethyl acetate in cyclohexane gradient over 60 minutes. Appropriate fractions were combined and evaporated in-vacuo to yield the title compound as an orange oil (720 mg).

Aufarbeitung

  1. stirringThe reaction was stirred at 60° C. for 3 hours
  2. stirringThe mixture was stirred at 60° C. for a further 2.5 hours
  3. customThe reaction mixture was evaporated in-vacuo
  4. customto yield a brown oil
  5. customThe resulting oil was partitioned between ethyl acetate (25 mL) and water/brine (1:1, 10 mL)
  6. customThe organic layer was separated
  7. customevaporated in-vacuo

Quellen und Nachweise

ORD-Eintrag
ord-cb9537c4a8304e8b8348316796ded83e
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09173872B2

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