3,4-dihydro-2H-pyran → 5-Bromo-4-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 2069556Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2069556
[Br:1][C:2]1[C:3]([F:11])=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.[CH2:12]1[CH2:17][O:16][CH:15]=[CH:14][CH2:13]1.C([O-])(O)=O.[Na+]>ClCCl.CC1C=CC(S(O)(=O)=O)=CC=1>[Br:1][C:2]1[C:3]([F:11])=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:15]1[CH2:14][CH2:13][CH2:12][CH2:17][O:16]1)[N:6]=[CH:5]2

Komponenten

6

Edukt 3

HCID 80803,4-dihydro-2H-pyranHCID 516892Sodium BicarbonateHCID 454803935-Bromo-4-fluoro-1H-indazole

Produkt 1

HCID 667933085-Bromo-4-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleAusbeute 79,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6101p-Toluenesulfonic acidKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a mixture of 5-bromo-4-fluoro-1H-indazole (50 g, 0.23 mol) and DHP (23 g, 0.28 mol) in dry dichloromethane (1000 mL) was added PTSA (2.2 g, 11.5 mmol) at room temperature. The resulting mixture was stirred overnight at that temperature. Upon completion, saturated aqueous NaHCO3 (100 mL) was added slowly into the reaction mixture. The organic layer was separated, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (0˜2% EtOAc in petroleum ether) and then re-crystallized from petroleum ether to afford the title compound (55 g). 1H NMR (300 MHz, DMSO-d6,): δ 8.28 (s, 1H), 7.58-7.66 (m, 2H), 5.89 (dd, 1H), 3.90-3.85 (m, 1H), 3.79-3.70 (m, 1H), 2.42-2.29 (m, 1H), 2.06-1.94 (m, 2H), 1.77-1.68 (m, 1H), 1.60-1.53 (m, 2H); LCMS: 299 (M+H)+.

Aufarbeitung

  1. customThe organic layer was separated
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by column chromatography on silica gel (0˜2% EtOAc in petroleum ether)
  5. customre-crystallized from petroleum ether

Quellen und Nachweise

ORD-Eintrag
ord-2d748d14ef6144f58d6e2ce03eb1b59c
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08299112B2

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