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

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 heated to reflux 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 H2O (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 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 mixture is heated
3. temperatureThe reaction continued refluxing for another 20 h
4. temperatureThe solution is cooled to rt
5. concentrationthe reaction is concentrated in vacuo
6. dissolutionThe purple residue is dissolved in H2O (60 mL)
7. filtrationthe slurry is filtered
8. temperaturewhile heating to 55° C
9. temperatureThe mixture is cooled
10. filtrationfiltered
11. concentrationthe organic layer is concentrated to a green oil
12. customThe crude material is chromatographed over 130 g slurry-packed silica
13. washeluting with 30% EtOAc/hexane

ORD-Eintrag

ord-629f49c159214c679e621136d2ede7eb

Quelldatensatz

uspto-grants-2005_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06911543B2