potassium;ethoxymethanedithioate

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

Procedure: To 17.3 g. of ethyl 3-amino-4-cyclohexylphenylglyoxylate in 11.1 ml. of concentrated hydrochloric acid and 20 g. of ice is added 4.1 g. of sodium nitrite in 2 ml. of water. This mixture is stirred for 10 min. and then added gradually to an ice cold solution of 10.3 g. of potassium ethyl xanthate in 14 ml. of water. The reaction is gradually heated over 45 minutes to 50° C. and stirred an additional 45 minutes. The mixture is then cooled, extracted with ether which is then washed with water, dilute sodium hydroxide and water, dried over sodium sulfate and evaporated in vacuo. The residue is dissolved in 35 ml. of boiling ethanol to which is added gradually 13 g. of potassium hydroxide. The reaction is refluxed an additional hour and then evaporated to dryness in vacuo. The residue is dissolved in water and extracted with ether. The alkaline phase is acidified with 6 N sulfuric acid and extracted with ether. The ether is washed with water, dried over sodium sulfate and evaporated to dryness to obtain 3-mercapto-4-cyclohexylphenylglyoxylic acid. of ice is added 4.1 g The reaction is gradually heated over 45 minutes to 50° C. stirred an additional 45 minutes The mixture is then cooled extracted with ether which is then washed with water, dilute sodium hydroxide and water dried over sodium sulfate evaporated in vacuo The residue is dissolved in 35 ml of boiling ethanol to which is added gradually 13 g The reaction is refluxed an additional hour evaporated to dryness in vacuo The residue is dissolved in water extracted with ether extracted with ether The ether is washed with water dried over sodium sulfate evaporated to dryness

Conditions: temp:78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(Methylthio)oxazolo[4,5-b]pyridine was prepared according to the procedures of Chu-Moyer and Berger (J. Org. Chem. 1995, 60, 5721-5725) with minor modifications. To a suspension of 2-amino-3-hydroxypyridine (2.8 g, 25 mmol) in EtOH (62 mL, 0.4 M) was added potassium ethyl xanthogenate (8.0 g, 50 mmol, 2 equiv). The reaction mixture was heated to reflux (78° C.) and stirred for a period of 18 hours. The reaction mixture was concentrated to dryness and the resulting residue was dissolved in water (70 mL). Upon acidification to pH 5 with glacial acetic acid, a large quantity of solid precipitated out. The suspension was filtered, washed with water (3×), and dried on the high-vac line overnight to afford 2-thiooxazolo[4,5-b]pyridine as a brown solid (3.3 g, 21.6 mmol, 86%). The reaction mixture was heated The reaction mixture was concentrated to dryness the resulting residue was dissolved in water (70 mL) Upon acidification to pH 5 with glacial acetic acid, a large quantity of solid precipitated out The suspension was filtered washed with water (3×) dried on the high-vac line overnight

Conditions: temp:78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(Methylthio)oxazolo[4,5-b]pyridine was prepared according to the procedures of Chu-Moyer and Berger (J. Org. Chem. 1995, 60, 5721-5725) with minor modifications. To a suspension of 2-amino-3-hydroxypyridine (2.8 g, 25 mmol) in EtOH (62 mL, 0.4 M) was added potassium ethyl xanthogenate (8.0 g, 50 mmol, 2 equiv). The reaction mixture was heated to reflux (78° C.) and stirred for a period of 18 hours. The reaction mixture was concentrated to dryness and the resulting residue was dissolved in water (70 mL). Upon acidification to pH 5 with glacial acetic acid, a large quantity of solid precipitated out. The suspension was filtered, washed with water (3×), and dried on the high-vac line overnight to afford 2-thiooxazolo[4,5-b]pyridine as a brown solid (3.3 g, 21.6 mmol, 86%). The reaction mixture was heated The reaction mixture was concentrated to dryness the resulting residue was dissolved in water (70 mL) Upon acidification to pH 5 with glacial acetic acid, a large quantity of solid precipitated out The suspension was filtered washed with water (3×) dried on the high-vac line overnight

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

Procedure: A mixture of 2-amino-4-methoxy-phenol (20.7 g, 0.15 mol), potassium O-ethylxanthate (26.2 g, 0.16 mol) and anhydrous pyridine was refluxed for two hours before it was cooled to room temperature and ice-cold 1N HCl (600 mL) was added. The precipitate was filtered, washed with water and dried in vacuo to give the title compound as a pale red solid (22.36 g): 1H NMR (CDCl3, 200 MHz): δ=7.20 (m, 1H), 6.78 (m, 2H), 3.82 (s, 3H). was refluxed for two hours before it The precipitate was filtered washed with water dried in vacuo

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

Procedure: Potassium ethyl xanthate (416 mg, 2.60 mmol) was added to a solution of 2-amino-4-bromophenol (244 mg, 1.30 mmol) in EtOH (3.24 mL). The reaction mixture was heated at reflux for 4 h. Upon cooling to RT the mixture was concentrated and the resulting residue was dissolved in water. Acetic acid was added until pH=5 and a white solid precipitated from the solution. The solid was filtered, washed with water and dried to afford 270 mg (90%) of a tan powder which was used without further purification: 1H NMR (d6-DMSO, 400 MHz) δ 14.02 (s, 1H), 7.47-7.38 (m, 3H); 13C (d6-DMSO, 400 MHz) δ 181.4, 148.1, 133.7, 127.1, 117.8, 118.8, 112.2; MS (Cl) m/z 229.8 (M−1); HPLC retention time=4.34 min. The reaction mixture was heated at reflux for 4 h was concentrated the resulting residue was dissolved in water Acetic acid was added until pH=5 a white solid precipitated from the solution The solid was filtered washed with water dried

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Chloro-5,8-dimethoxy-4-nitro-9H-thioxanthen-9-one is prepared as follows: A solution of 9.5 g (0.048 mol) of 2-amino-3,6-dimethoxybenzoic acid [P. K. Bannerjee and D. N. Chaudhury, J. Indian Chem. Soc., 86 (4), 257 (1959)], 4.6 ml (0.11 mol) of 50% aqueous NaOH, 60 ml of H2O, and 3.3 g (0.048 mol) of NaNO2 was added slowly to a mixture of 15 ml of concentrated HCl and 20 g of ice chips which had been previously cooled in a salt-ice bath to -5° C. Good stirring was maintained throughout the addition and the temperature was kept below 5° C. After the addition was complete, the mixture was stirred to 0° C. for one hour, neutralized (pH 5.5) with potassium acetate, and added while cold in a thin stream to an 80° C. solution of 22.2 g (0.15 mol) of potassium ethyl xanthate in 75 ml of H2O under N2. Copious N2 evolution (foaming) occurred during the addition, and heat was applied as needed to maintain the temperature at 75°-80° C. The reaction mixture, under N2, was cooled to 20° C. and acidified (pH 3) with concentrated HCl. The oily material which separated was extracted into CH2Cl2 (2X), keeping contact with air to a minimum. The extracts were combined, dried under N2 (MgSO4), and concentrated on a steam bath to a brown oil using a stream of N2. The crude 2,5-dimethoxy-6-thiobenzoic acid was immediately dissolved in 40 ml of hot anhydrous EtOH and added to a premixed, 25° C. mixture of 9.2 g (0.048 mol) of 2,4-dichloronitrobenzene in sodium ethoxide [2.2 g (0.096 g atom) of sodium spheres dissolved in 90 ml of anhydrous EtOH]. The resulting suspension was heated under reflux for 16 hours, concentrated to dryness in vacuo and taken up in 250 ml of ether and 250 ml of H2O. The layers were separated and the aqueous layer was extracted twice with ether to remove organic soluble impurities, and made acidic (pH 1) with concentrated HCl. The solid which formed was collected, dried, and recrystallized from EtOH to give a first crop of product. The mother liquor was concentrated to dryness in vacuo and the residue was crystallized from CH3CN to give a second crop of product. The mother liquor was concentrated to dryness in vacuo and the residue was flash chromatographed over 500 g of silica gel, eluting with CH2Cl2 /MeOH (15/1). Combination of the appropriate fractions, concentration to dryness in vacuo, and crystallization of the residue from acetonitrile provided a third crop of product. All crops were combined to give 7.8 g of 2-[(5-chloro-2-nitrophenyl)-thio]-3,6-dimethoxybenzoic acid, mp 218°-220° C. was maintained throughout the addition was kept below 5° C After the addition the mixture was stirred to 0° C. for one hour heat to maintain the temperature at 75°-80° C The reaction mixture, under N2, was cooled to 20° C. The oily material which separated was extracted into CH2Cl2 (2X) dried under N2 (MgSO4) concentrated on a steam bath to a brown oil The crude 2,5-dimethoxy-6-thiobenzoic acid was immediately dissolved in 40 ml of hot anhydrous EtOH The resulting suspension was heated under reflux for 16 hours concentrated to dryness in vacuo The layers were separated the aqueous layer was extracted twice with ether to remove organic soluble impurities The solid which formed was collected dried recrystallized from EtOH to give a first crop of product The mother liquor was concentrated to dryness in vacuo the residue was crystallized from CH3CN to give a second crop of product The mother liquor was concentrated to dryness in vacuo chromatographed over 500 g of silica gel eluting with CH2Cl2 /MeOH (15/1) Combination of the appropriate fractions, concentration to dryness in vacuo, and crystallization of the residue from acetonitrile provided a third crop of product

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

Procedure: To a mixture of N-[2-(bis-{2-[2-(2-chloro-acetylamino)-2-methyl-propionylamino]-ethyl}-amino)ethyl]-2-(2-chloro-acetylamino)-2-methyl-propionamide (1.00 g; 1.54 mmol) and 20 mL acetonitrile was added O-ethyl xanthic acid potassium salt (0.761 g; 4.75 mmol). After stirring the mixture at room temperature for 5 hr, additional O-ethyl xanthic acid potassium salt (0.370 g; 2.31 mmol) was added. After stirring for an additional 5 hours at room temperature, the mixture was filtered. The filtrate was concentrated under reduced pressure to to afford 1.20 g (87%) of the tris(ring-opened AzTC)amine as a red solid. After stirring for an additional 5 hours at room temperature the mixture was filtered The filtrate was concentrated under reduced pressure

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

Procedure: To a solution of 2-(1-bromo-ethyl)-4,4dimethyl-4H-oxazol-5-one (3.00 g; 13.6 mmol) and 50 mL acetonitrile was added O-ethyl xanthic acid potassium salt (2.18 g; 13.6 mmol). The mixture was stirred under a nitrogen atmosphere at room temperature for 5 hours. The reaction mixture was filtered and the solid was washed with 10 mL acetontrile 10 mL. The combined filtrate was concentrated under reduced pressure to afford 2.89 g (81%) of dithiocarbonic acid S-[1-(4,4-dimethyl-5-oxo-4,5-dihydro-oxazol-2-yl)-ethyl] ester O-ethyl ester as a yellow oil. The reaction mixture was filtered the solid was washed with 10 mL acetontrile 10 mL The combined filtrate was concentrated under reduced pressure

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

Procedure: To a solution of 2-chloromethyl-4,4-dimethyl4H-oxazol-5-one (15.67 g, 97 mmol) and 125 mL acetonitrile was added O-ethyl xanthic acid potassium salt (15.55 g; 97 mmol). The mixture was stirred under a nitrogen atmosphere at room temperature for 16 hours. The reaction mixture was filtered and the solid was washed with 50 mL acetonitrile. The combined filtrate was concentrated under reduced pressure to afford 21.79 g (91%) of AzTC as a yellow crystalline solid. The reaction mixture was filtered the solid was washed with 50 mL acetonitrile The combined filtrate was concentrated under reduced pressure to afford 21.79 g (91%) of AzTC as a yellow crystalline solid

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

Procedure: A solution of bromoacetonitrile (12.4 g) and potassium O-ethyl dithiocarbonate (16.0 g) in ethanol (200 mL) were allowed to stir at room temperature for 16 hours. The reaction was diluted with water (100 mL) and the organics extracted with diethyl ether. The combined organic layers were washed twice with water, then brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue purified by column chromatography (silica-gel 60, 70-230 mesh) eluting with 4:6 ethyl acetate:petroleum spirit 40-60° C. to afford the title compound as a yellow oil (14.6 g, 90.7%). 1H-nmr (CDCl3) δ 1.48 (t, 3H); 3.88 (s, 2H); 4.72 (q, 2H). 13C-nmr (CDCl3) δ 13.7, 21.3, 71.5, 115.7, 209.2. the organics extracted with diethyl ether The combined organic layers were washed twice with water brine and dried over anhydrous magnesium sulfate The solvent was evaporated the residue purified by column chromatography (silica-gel 60, 70-230 mesh) eluting with 4:6 ethyl acetate

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

Procedure: N-[2-(6-Amino-7-hydroxy-2,3-dihydro-1H-inden-1-yl)ethyl]acetamide hydrochloride (100 mg, 0.369 mmol) and potassium O-ethyl dithiocarbonate (65.1 mg, 0.406 mmol) were heated under reflux in pyridine (1 mL) for 2 hr. The reaction solution was diluted with ethyl acetate, washed with 1N hydrochloric acid and saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/methanol=100/0-90/10) to give the title compound (64.8 mg, yield 64%). washed with 1N hydrochloric acid and saturated brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography (ethyl acetate/methanol=100/0-90/10)

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

Procedure: 5-Bromo-pyrimidine-2,4-diamine (2.0 g, 10.58 mmol) [prepared in a manner similar to English et. al. J. Am. Chem. Soc. 1946, 68, 453-458] and O-ethylxanthic acid potassium salt (3.39 g, 21.16 mmol) was heated in DMF (25 mL) to 140° C. After 5 h the reaction was cooled to ambient temperature and 25 mL of water was added. The pH was then adjusted to 5.0 using 1 N HCl. A red precipitate formed and was collected by filtration, yielding 900 mg (30%) of a solid: 1H NMR (400 MHz, d6-DMSO) δ 13.85 (s, 1H), 8.33 (br s, 1H), 6.90 (s 2H). A red precipitate formed was collected by filtration