Ammonium Chloride → tert-butyl N-[7-bromo-2-methylthiopyrazolo[1,5-a]pyridin-3-yl]carbamate

HRID 1181883

Reaktionsgleichung

Reaktionsgleichung von HRID 1181883
[CH3:1][S:2][C:3]1[C:11]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][N:5]2[N:4]=1.C([Li])CCC.[Br:25]C(Cl)(Cl)C(Br)(Cl)Cl.[Cl-].[NH4+]>O1CCCC1.CCCCCC>[Br:25][C:10]1[N:5]2[N:4]=[C:3]([S:2][CH3:1])[C:11]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[C:6]2[CH:7]=[CH:8][CH:9]=1

Komponenten

7

Edukt 4

HCID 25517Ammonium ChlorideHCID 694261,2-Dibromo-1,1,2,2-tetrachloroethaneHCID 21984591tert-butyl N-[2-methylthiopyrazolo[1,5-a]pyridin-3-yl]carbamateHCID 178418339Butyllithium

Produkt 1

HCID 21984585tert-butyl N-[7-bromo-2-methylthiopyrazolo[1,5-a]pyridin-3-yl]carbamate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 8058HexaneLösungsmittel

Versuchsvorschrift

After dissolving tert-butyl N-[2-methylthiopyrazolo[1,5-a]pyridin-3-yl]carbamate (220 mg) in tetrahydrofuran (3 mL), a solution of n-butyllithium in hexane (1.6 M; 1.51 mL) was added dropwise at −78° C. under a nitrogen stream, and the mixture was stirred for 30 minutes. A solution of 1,2-dibromo-1,1,2,2-tetrachloroethane (384 mg) in tetrahydrofuran (2 mL) was added to the reaction mixture, and stirring was continued for 30 minutes. Saturated aqueous ammonium chloride was added to the reaction mixture, the temperature was raised to room temperature, extraction was performed with ethyl acetate and the extract was washed with water and brine. After drying over anhydrous magnesium sulfate and filtration, the solvent was concentrated under reduced pressure, the residue was purified by silica gel column chromatography, and tert-butyl N-[7-bromo-2-methylthiopyrazolo[1,5-a]pyridin-3-yl]carbamate was obtained from the n-hexane:ethyl acetate (10:1) fraction as yellow crystals. After dissolving this in 1,2-dimethoxyethane (6 mL) and water (1 mL), 2,4-dichlorophenylboric acid (191 mg), tetrakis(triphenylphosphine)palladium (0) complex (116 mg) and barium hydroxide octahydrate (315 mg) were added and the mixture was heated and stirred at 80° C. for 4 hours under a nitrogen stream. Water was added to the reaction mixture, extraction was performed with ethyl acetate and the extract was washed with brine. After drying over anhydrous magnesium sulfate and filtration, the solvent was concentrated under reduced pressure, the residue was purified by silica gel column chromatography, and the title compound (160 mg) was obtained from the n-hexane:ethyl acetate (20:1) fraction as a yellow oil.

Aufarbeitung

  1. stirringstirring
  2. waitwas continued for 30 minutes
  3. extractionextraction
  4. washthe extract was washed with water and brine
  5. dry with materialAfter drying over anhydrous magnesium sulfate and filtration
  6. concentrationthe solvent was concentrated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-cdbebab74a784611bba6c645e04066cf
Quelldatensatz
uspto-grants-2007_10
Patentnummer
US07285666B2

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