Hydrochloric Acid → Thieno[2,3-b]pyridine-5-carbonitrile

Temperatur

80 °C

3,3-Dimethyl-2-formyl propionitrile sodium (3.33 g, 20.2 mmol) can readily be prepared from the method described by Bertz, S. H., et al., J. Org. Chem., 47, 2216–2217 (1982). 3,3-Dimethyl-2-formyl propionitrile sodium is dissolved in MeOH (40 mL), and concentrated HCl (4 mL) and the hexachlorostannate salt of 2-aminothiophene (10.04 g, 19.1 mmol) in MeOH (130 mL) is slowly added drop-wise to the mixture. Following addition, the mixture is refluxed in an oil bath (80° C.) for 4 h, and then MeOH (10 mL) and concentrated HCl (10 mL) are added. The reaction continued refluxing for another 20 h. The solution is cooled to rt, and the reaction is concentrated in vacuo. The purple residue is dissolved in water (60 mL), and the slurry is filtered. The cake is pulverized and stirred vigorously with 5% MeOH/CHCl3 (105 mL) while heating to 55° C. The mixture is cooled and filtered, and the organic layer is concentrated to a green oil. The crude material is chromatographed over 130 g slurry-packed silica, eluting with 30% EtOAc/hexane. The fractions with the desired compound are collected and concentrated to afford thieno[2,3-b]pyridine-5-carbonitrile (C105) as a pale yellow solid (24% yield). HRMS (FAB) calculated for C8H4N2S+H: 161.0173, found 161.0173 (M+H)+.

1. additionaddition
2. temperatureThe reaction continued refluxing for another 20 h
3. temperatureThe solution is cooled to rt
4. concentrationthe reaction is concentrated in vacuo
5. dissolutionThe purple residue is dissolved in water (60 mL)
6. filtrationthe slurry is filtered
7. temperaturewhile heating to 55° C
8. temperatureThe mixture is cooled
9. filtrationfiltered
10. concentrationthe organic layer is concentrated to a green oil
11. customThe crude material is chromatographed over 130 g slurry-packed silica
12. washeluting with 30% EtOAc/hexane
13. customThe fractions with the desired compound are collected
14. concentrationconcentrated

ORD-Eintrag

ord-bcdc7f4185f543cbad432f6fd4c9e5ae

Quelldatensatz

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07067515B2