Tetrahydrofuran → 2-Tert-butyl-6-(2,5-difluoro-phenylethynyl)-[1,2,4]triazolo[1,5-a]pyrimidine

HRID 2042193Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2042193
[C:1]([C:5]1[N:19]=[C:8]2[N:9]=[CH:10][C:11]([C:13]#[C:14][Si](C)(C)C)=[CH:12][N:7]2[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[F:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=1I.CCN(CC)CC.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([C:5]1[N:19]=[C:8]2[N:9]=[CH:10][C:11]([C:13]#[C:14][C:25]3[CH:26]=[C:21]([F:20])[CH:22]=[CH:23][C:24]=3[F:27])=[CH:12][N:7]2[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

Komponenten

10

Edukt 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 2230841,4-Difluoro-2-iodobenzeneHCID 2724141Tetrabutylammonium FluorideHCID 583166982-tert-Butyl-6-trimethylsilanylethynyl-[1,2,4]triazolo[1,5-a]pyrimidine

Produkt 1

HCID 532475722-Tert-butyl-6-(2,5-difluoro-phenylethynyl)-[1,2,4]triazolo[1,5-a]pyrimidineAusbeute 64 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11776TriphenylphosphineKatalysatorHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

2-tert-Butyl-6-trimethylsilanylethynyl-[1,2,4]triazolo[1,5-a]pyrimidine (example 43, step 1) (100 mg, 0.37 mmol) was dissolved in DMF (1 ml). 1,4-Difluoro-2-iodobenzene (176 mg, 0.73 mmol, 2 equiv.), Et3N (150 μl, 1.1 mmol, 3 equiv.), Bis-(triphenylphosphine)-palladium (II) dichloride (13 mg, 0.02 mmol, 0.05 equiv.), triphenylphosphine (3 mg, 0.011 mmol, 0.03 equiv.) and copper (I) iodide (2 mg, 0.011, 0.03 equiv.) were added under nitrogen and the mixture was heated to 80° C. TBAF 1M in THF (440 μl, 0.44 mmol, 1.2 equiv.) was added dropwise in 20 minutes at 80° C. The reaction mixture was stirred for 5 minutes at 80° C. The reaction mixture was evaporated and extracted with saturated NaHCO3 solution and two times with a small volume of dichloromethane. The crude product was purified by flash chromatography by directly loading the dichloromethane layers onto a 20 g silica gel column and eluting with heptane:ethyl acetate 100:0->50:50. The desired 2-tert-butyl-6-(2,5-difluoro-phenylethynyl)-[1,2,4]triazolo[1,5-a]pyrimidine (73 mg, 64% yield) was obtained as a light yellow solid, MS: m/e=313.1 (M+H+).

Aufarbeitung

  1. customThe reaction mixture was evaporated
  2. extractionextracted with saturated NaHCO3 solution and two times with a small volume of dichloromethane
  3. customThe crude product was purified by flash chromatography
  4. washeluting with heptane:ethyl acetate 100:0->50:50

Quellen und Nachweise

ORD-Eintrag
ord-a7555400beba4298b791a61b3375761d
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08586581B2

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