propanethioamide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of ethyl 2-chloroacetoacetate (2.00 g, 10.04 mmol) and thiopropionamide (1.00 g, 11.22 mmol) in ethanol (100 mL) was heated at reflux overnight. The solvent was evaporated and dichloromethane (100 mL) added. The solution was washed with water (2×100 mL) and brine (100 mL), dried (MgSO4), filtered, evaporated and the concentrate was chromatographed over silica gel (10% ethyl acetate/hexanes) to give 2-ethyl-4-methylthiazole-5-carboxylic acid ethyl ester (1.63 g, 81% yield) as a colorless liquid. at reflux overnight The solvent was evaporated dichloromethane (100 mL) added The solution was washed with water (2×100 mL) and brine (100 mL) dried (MgSO4) filtered evaporated the concentrate was chromatographed over silica gel (10% ethyl acetate/hexanes)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of ethyl 2-chloroacetoacetate (2.00 g, 10.04 mmol) and thiopropionamide (1.00 g, 11.22 mmol) in ethanol (100 mL) was heated at reflux overnight. The solvent was evaporated and dichloromethane (100 mL) added. The solution was washed with water (2×100 mL) and brine (100 mL), dried (MgSO4), filtered, evaporated and the concentrate was chromatographed over silica gel (10% ethyl acetate/hexanes) to give 2-ethyl-4-methylthiazole-5-carboxylic acid ethyl ester (1.63 g, 81% yield) as a colorless liquid. at reflux overnight The solvent was evaporated dichloromethane (100 mL) added The solution was washed with water (2×100 mL) and brine (100 mL) dried (MgSO4) filtered evaporated the concentrate was chromatographed over silica gel (10% ethyl acetate/hexanes)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of propiothioamide (892 mg, 10 mmol) and 2-bromophenylnaphthalene (2.21 g, 10 mmol) in chloroform (80 mL) was heated at 80° C. for 2 h. After cooling, the mixture was poured into diethyl ether (100 mL) and cooled at 0° C. for 1 h. The resulting precipitate was corrected by filtration and dried under reduced pressure to give 2.85 g (92%) of the title compound as a colorless powder. MS (ESI) m/z 230 [M+H]+. After cooling cooled at 0° C. for 1 h The resulting precipitate was corrected by filtration dried under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of propiothioamide (892 mg, 10 mmol) and 2-bromophenylnaphthalene (2.21 g, 10 mmol) in chloroform (80 mL) was heated at 80° C. for 2 h. After cooling, the mixture was poured into diethyl ether (100 mL) and cooled at 0° C. for 1 h. The resulting precipitate was corrected by filtration and dried under reduced pressure to give 2.85 g (92%) of the title compound as a colorless powder. MS (ESI) m/z 230 [M+H]+. After cooling cooled at 0° C. for 1 h The resulting precipitate was corrected by filtration dried under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-bromo-3-(2-bromoacetyl)-2-(4-methanesulfonylbenzyl)-4-phenyl-2H-isoquinolin-1-one (300 mg), thiopropionamide (70 mg), THF (3 ml) and ethanol (3 ml) was stirred at 80° C. for 12 hrs. The reaction mixture was concentrated under reduced pressure and saturated aqueous sodium hydrogen carbonate was added to the residue. The mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1-hexane:ethyl acetate=1:2) and recrystallized (ethyl acetate-hexane) to give the title compound (100 mg). The reaction mixture was concentrated under reduced pressure and saturated aqueous sodium hydrogen carbonate was added to the residue The mixture was extracted with ethyl acetate The organic layer was washed with water and saturated brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1-hexane:ethyl acetate=1:2) recrystallized (ethyl acetate-hexane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.40 g (1.47 mmol) 5-bromo-azepan-4-one hydrobromide, 0.13 g (1.47 mmol) thiopropionamide and 3 mL ethanol were stirred under reflux for 3 hours. The reaction was allowed to cool to RT and was filtered. The filtrate was concentrated to dryness and dried. under reflux for 3 hours was filtered The filtrate was concentrated to dryness dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound is prepared by reacting 5-bromo-4-oxo-4,5,6,7-tetrahydro-indole 1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester with thiopropionamide essentially according to the procedures described in Example 15, Step 3. 1H NMR (CDCl3) 1.33-1.42 (m, 6H), 2.80-2.90 (m, 2H), 2.98-3.10 (m, 4H), 2.37 (q, 2H), 7.24 (s, 1H), 8.60 (s, 1H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound is prepared by reacting 5-bromo-4-oxo-4,5,6,7-tetrahydro-indole 1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester with thiopropionamide essentially according to the procedures described in Example 15, Step 3. 1H NMR (CDCl3) 1.33-1.42 (m, 6H), 2.80-2.90 (m, 2H), 2.98-3.10 (m, 4H), 2.37 (q, 2H), 7.24 (s, 1H), 8.60 (s, 1H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl 3-bromo-2-oxopropanoate (24.7 mL) was added dropwise over 10 min to a solution of propanethioamide [Carboxylic Acid 1, step a] (15.8 g) in ethanol (150 mL) at 0-10° C. under nitrogen. When the addition was complete the mixture was stirred at ambient temperature for 18 hours. The mixture was concentrated in vacuo, the residue diluted with water and extracted into ethyl acetate (×3). The combined extracts were washed with brine, dried over magnesium sulfate, filtered and the solvent removed. The crude product was purified by flash silica chromatography, elution gradient 10, 15 and 20% ethyl acetate in isohexane. Fractions containing the product were evaporated to dryness to afford the subtitled compound as a pale green solid. Yield 16.0 g. When the addition The mixture was concentrated in vacuo the residue diluted with water extracted into ethyl acetate (×3) The combined extracts were washed with brine dried over magnesium sulfate filtered the solvent removed The crude product was purified by flash silica chromatography, elution gradient 10, 15 and 20% ethyl acetate in isohexane Fractions containing the product were evaporated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl 3-bromo-2-oxopropanoate (24.7 mL) was added dropwise over 10 min to a solution of propanethioamide [Carboxylic Acid 1, step a] (15.8 g) in ethanol (150 mL) at 0-10° C. under nitrogen. When the addition was complete the mixture was stirred at ambient temperature for 18 hours. The mixture was concentrated in vacuo, the residue diluted with water and extracted into ethyl acetate (×3). The combined extracts were washed with brine, dried over magnesium sulfate, filtered and the solvent removed. The crude product was purified by flash silica chromatography, elution gradient 10, 15 and 20% ethyl acetate in isohexane. Fractions containing the product were evaporated to dryness to afford the subtitled compound as a pale green solid. Yield 16.0 g. When the addition The mixture was concentrated in vacuo the residue diluted with water extracted into ethyl acetate (×3) The combined extracts were washed with brine dried over magnesium sulfate filtered the solvent removed The crude product was purified by flash silica chromatography, elution gradient 10, 15 and 20% ethyl acetate in isohexane Fractions containing the product were evaporated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: a solution of 26 gm of thiopropionamide in 100 cc of ethanol is mixed with a solution of 36.5 gm of ethyl 2-chloro-3-oxo-propionate in 50 cc of ethanol. The reaction mixture is left in contact overnight, then the alcohol is evaporated off. The residue is dissolved in ether, the ethereal phase is washed with an aqueous 20% sodium carbonate solution, then with water. The oil obtained is distilled and the fraction coming off at 80° C. to 90° C. under a pressure of 0.5 mm is recovered. This fraction is saponified with an alcoholic solution of potassium hydroxide, then acidified and recrystallized from toluene. 2-Ethyl-5-thiazolecarboxylic acid is obtained in the form of colorless crystals, soluble in ethanol and sodium hydroxide, insoluble in water, melting at 157° C. the alcohol is evaporated off The residue is dissolved in ether the ethereal phase is washed with an aqueous 20% sodium carbonate solution The oil obtained is distilled coming off at 80° C. to 90° C. under a pressure of 0.5 mm is recovered recrystallized from toluene

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of ethyl γ-chloro-α-oximinoacetoacetate (2.00 g, 10.3 mmol) and thiopropionamide (0.92 g, 10.3 mmol) in dry benzene (15 mL) was heated at reflux. After 4 hours the reaction mixture was poured onto NaHCO3 (sat. aq., 50 mL), The resulting mixture was extracted with ethyl acetate (2×50 mL), and the combined extracts dried over MgSO4 and evaporated under reduced pressure. Flash chromatography (ethyl acetate:hexane 1:4) then afforded impure ethyl α-oximino-2-ethylthiazole-4-acetate (0.83 g). The crude oxime was dissolved in methanol (25 mL) and formic acid (50% aq., 10 mL) was added. The mixture was cooled to 0° C. and zinc dust (1.00 g, 15.3 mmol) was added in portions over 30 mins. The reaction mixture was allowed to warm to room temperature and stirred for 6 hours. The solution was then filtered, basified to pH 9 with solid NaHCO3, and extracted with ethyl acetate (3×80 mL). The combined extracts were dried (MgSO4) and evaporated to afford D/L-2-ethylthiazol-4-ylglycine ethyl ester (0.56 g, 2.6 mmol). at reflux After 4 hours the reaction mixture was poured onto NaHCO3 (sat. aq., 50 mL) The resulting mixture was extracted with ethyl acetate (2×50 mL) the combined extracts dried over MgSO4 evaporated under reduced pressure