Cesium carbonate → 1-(2,2-Dimethoxyethyl)-5-iodo-1H-indazole

HRID 2387506

Reaktionsgleichung

[I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.[CH3:11][O:12][CH:13]([O:16][CH3:17])[CH2:14]Br.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.O.CCOC(C)=O>[CH3:11][O:12][CH:13]([O:16][CH3:17])[CH2:14][N:7]1[C:8]2[C:4](=[CH:3][C:2]([I:1])=[CH:10][CH:9]=2)[CH:5]=[N:6]1

Komponenten

Reaktionsbedingungen

Temperatur: 40 °C

Versuchsvorschrift

To a solution of 5-iodio-1H-indazole (8.28 g, 33.9 mmol) in DMSO (104 mL) was added 2-bromoacetaldehyde dimethyl acetal (7.9 mL, 68 mmol) and Cs2CO3 (44.1 g, 136 mmol). The reaction mixture was stirred at 40° C. for 18 h; then the reaction mixture was diluted with H2O (100 mL) and EtOAc (175 mL). The partitioned material was extracted with EtOAc (4×175 mL). The organics were washed with brine (2×100 mL), dried (Na2SO4), filtered, and concentrated. Purification by flash chromatography (silica gel, hexanes with 0.1% Et3N/EtOAc with 0.1% Et3N, 100:0 to 90:10) gave the title compound (4.49 g, 46%) as a light orange powder. 1H NMR (500 MHz, CDCl3) δ 8.07 (d, J=1.0 Hz, 1H), 7.92 (d, J=0.5 Hz, 1H), 7.60 (dd, J=9.0, 1.5 Hz, 1H), 7.28 (d, J=9.0 Hz, 1H), 4.71 (t, J=5.5 Hz, 1H), 4.44 (d, J=5.5 Hz, 2H), 3.33 (s, 6H).

Aufarbeitung

extractionThe partitioned material was extracted with EtOAc (4×175 mL)
washThe organics were washed with brine (2×100 mL)
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customPurification by flash chromatography (silica gel, hexanes with 0.1% Et3N/EtOAc with 0.1% Et3N, 100:0 to 90:10)

Quellen und Nachweise

ORD-Eintrag: ord-26f0c7ecfb054d2bb9fb10b7b3c24e90
Quelldatensatz: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08268868B2

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