2-(Pyridin-2-ylthio)ethanamine → N-(2-(pyridin-2-ylsulfanyl)ethyl)thioacetamide

To a mixture of 2-aminoethanethiol hydrochloride (4.07 g, 35.6 mmol) in dioxane (75 mL) at 50° C., add sodium hydride (60% in mineral oil, 2.84 g, 71.0 mmol) at room temperature under nitrogen. Allow the reaction to stir for 5 minutes and add 2-chloropyridine (3.5 mL, 37 mmol) to the mixture. Reflux the mixture for 24 hours and cool to room temperature. Add water (100 mL), and methylene chloride (300 mL) to this mixture. Extract the aqueous layer with methylene chloride (3×50 mL). Wash the combined organic phase with brine (200 mL), dry over magnesium sulfate, filter and concentrate to an orange oil. Flash chromatography on silica gel eluting with 50% (80:18:12 CHCl3/MeOH/concentrated NH4OH)/methylene chloride affords the title compound as a yellow oil (1.67 g, 30%). 1H NMR (CDCl3) δ 8.43 (m, 1H), 7.44 (m, 1H), 7.21 (m, 1H), 6.97 (m, 1H), 3.30 (m, 2H), 3.02 (m, 2H); MS (ES) m/z:═155 [C7H10N2S+H]+. Add 2-thioacetyl-isoindole-1,3-dione (0.7 g, 3.2 mmol) to a solution of 2-(pyridin-2-ylsulfanyl)ethylamine (0.5 g, 3.2 mmol) in CHCl3 (20 mL) at 0° C. After 15 minutes, concentrate and purify the residue by flash chromatography on silica gel eluting with 40% EtOAc/Hex containing 2% NH4OH to afford N-(2-(pyridin-2-ylsulfanyl)ethyl)thioacetamide (0.4 g, 58%) as a pale yellow oil. 1H NMR (CDCl3) δ 10.26 (br s, 1H), 8.41-8.43 (m, 1H), 7.57 (dt, J=7.35 Hz, J=1.8 Hz, 1H), 7.31 (dd, J=8.10 Hz, J=0.96 Hz, 1H), 7.09-7.13 (m, 1H), 3.87-3.92 (m, 2H), 3.40-3.43 (m, 2H), 2.53 (s, 3H); MS (APCI): m/z 213 (M+H).

1. customat 0° C
2. concentrationconcentrate
3. custompurify the residue by flash chromatography on silica gel eluting with 40% EtOAc/Hex
4. additioncontaining 2% NH4OH

ORD record

ord-e4186d779b8f4d9481f84cdcfb23036d

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07378447B2