Reaktion #2165864

Reaktionsgleichung

potassium carbonate

[3-(N′-benzhydrylidene-hydrazino)-thiophen-2-yl]-(1-benzyloxymethyl-6-methoxy-1H-benzoimidazol-2-yl)-methanone

hydrochloric acid

ethanol

→

6-methoxy-2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-benzoimidazole

Lösungsmittel

water

ethyl acetate heptane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto cool to ambient temperature
2. 2
   ExtraktionThe mixture is extracted with ethyl acetate
3. 3
   Waschenthe combined extracts washed with water and brine successively
4. 4
   TrocknenThe organic layer is dried over potassium carbonate
5. 5
   Einengenconcentrated under reduced pressure
6. 6
   Sonstigeto give a brown solid
7. 7
   SonstigeThe solid is chromatographed on silica
8. 8
   WaschenStep gradient elution with 70% ethyl acetate/heptane, 80% ethyl acetate/heptane, and 90% ethyl acetate/heptane
9. 9
   Sonstigeprovided an orange solid

Vorschrift

A mixture of [3-(N′-benzhydrylidene-hydrazino)-thiophen-2-yl]-(1-benzyloxymethyl-6-methoxy-1H-benzoimidazol-2-yl)-methanone (300 mg, 0.553 mmol, Example 2C), concentrated hydrochloric acid (4 mL), and ethanol (12 mL) is heated at 75° C. with stirring for 260 minutes. The reaction is allowed to cool to ambient temperature, diluted with water (40 mL), and basified with 5% aqueous potassium carbonate. The mixture is extracted with ethyl acetate and the combined extracts washed with water and brine successively. The organic layer is dried over potassium carbonate and concentrated under reduced pressure to give a brown solid. The solid is chromatographed on silica. Step gradient elution with 70% ethyl acetate/heptane, 80% ethyl acetate/heptane, and 90% ethyl acetate/heptane provided an orange solid. Trituration with ethyl acetate/heptane gave 6-methoxy-2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-benzoimidazole as a beige powder: TLC Rf 0.28 (silica, 75% ethyl acetate/heptane); LC/MS: M+H 241.0, RT=2.15 minutes; 1H NMR [(CD3)2SO), 300 MHz]: two species observed (ca. 60:40), presumed to be slowly exchanging imidazole tautomers, with chemical shifts of resolved resonances reported as major (minor); δ 13.48 (13.51) brs (1H; NH of benzimidazole), 12.79 brs (1H; NH of pyrazole), 7.77 d (1H, J=5 Hz; H-α of thiophene), 7.57 (7.35) d (1H, J=8.5 Hz; H-7 of benzimidazole), 7.20 d (1H, J=5 Hz; H-β of thiophene), 6.96 (7.25) d (1H, J=2 Hz; H-4 of benzimidazole), 6.82 m (1H; H-6 of benzimidazole), 3.80 (3.32) s (3H; methoxy). Chemical shifts are referenced to internal dimethyl sulfoxide-D5 (δ 2.50).

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