2-methylsulfanyl-4,5-dihydro-1,3-thiazole

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a suspension of 2-amino-4-methyl-5-(4-methylpyridin-2-yl)-thiazole and 2-(methylthio)-2-thiazoline (127 mg) in methoxyethanol (2 ml) was added a solution of hydrogen chloride in 1,4-dioxane (4N, 0.23 ml). The mixture was refluxed for 20 hours, poured into a saturated aqueous sodium hydrogencarbonate solution and extracted with ethyl acetate twice. The combined organic layer was washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography (silica gel 25 g, 5% methanol in dichloromethane) and recrystallized from chloroform (1 ml)-diisopropyl ether (3 ml) to give 2-(4-methyl-5-(4-methylpyridin-2-yl)thiazol-2-ylamino)-2-thiazoline (110 mg). The mixture was refluxed for 20 hours extracted with ethyl acetate twice The combined organic layer was washed with brine dried over sodium sulfate evaporated under reduced pressure The residue was purified by column chromatography (silica gel 25 g, 5% methanol in dichloromethane) recrystallized from chloroform (1 ml)-diisopropyl ether (3 ml)

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

Procedure: To a suspension of 2-amino-4-methyl-5-(4-methylpyridin-2-yl)-thiazole and 2-(methylthio)-2-thiazoline (127 mg) in methoxyethanol (2 ml) was added a solution of hydrogen chloride in 1,4-dioxane (4N, 0.23 ml). The mixture was refluxed for 20 hours, poured into a saturated aqueous sodium hydrogencarbonate solution and extracted with ethyl acetate twice. The combined organic layer was washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography (silica gel 25 g, 5% methanol in dichloromethane) and recrystallized from chloroform (1 ml)-diisopropyl ether (3 ml) to give 2-(4-methyl-5-(4-methylpyridin-2-yl)thiazol-2-ylamino)-2-thiazoline (110 mg). The mixture was refluxed for 20 hours extracted with ethyl acetate twice The combined organic layer was washed with brine dried over sodium sulfate evaporated under reduced pressure The residue was purified by column chromatography (silica gel 25 g, 5% methanol in dichloromethane) recrystallized from chloroform (1 ml)-diisopropyl ether (3 ml)

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

Procedure: A mixture of ethyl carbazate (23.4 g), 2-(methylthio)-2-thiazoline (25 g) and ethanol (250 ml) was heated to reflux for 3 days. It was then stirred at room temperature for 2 days. The precipitate was collected by filtration and washed with ethanol to obtain the title compound (9.05 g). was heated to reflux for 3 days The precipitate was collected by filtration washed with ethanol

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

Procedure: A mixture of ethyl carbazate (23.4 g), 2-(methylthio)-2-thiazoline (25 g) and ethanol (250 ml) was heated to reflux for 3 days. It was then stirred at room temperature for 2 days. The precipitate was collected by filtration and washed with ethanol to obtain the title compound (9.05 g). was heated to reflux for 3 days The precipitate was collected by filtration washed with ethanol

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

Procedure: To a solution of lithium diisopropylamide (LDA), prepared from n-BuLi (106.6 ml, 0.16M) and diisopropylamine (16.7 g, 23.1 ml, 0.16M), in dry THF (100 ml) was added under N2 at -10° C., 5-methylisoxazole (6.8 g, 0.08M). The resultant yellow suspension was mechanically stirred at -10° C. for 30 min before the 4,5-dihydro-2-methylthiothiazole (11 g, 0.08M) was added dropwise. After the addition was complete, an orange oil separated, and the mixture was allowed to warm to ambient over a period of 20 hr. A mixture of MeOH (60 ml) and glacial acetic acid (4.5 ml, 0.08M) was slowly added and the resultant reddish solution was stirred at ambient overnight. The solvents were evaporated in vacuo, and the residual oil was flash column chromatographed on silica gel (EM-60) with 30% MeOH in CH2Cl2 as the eluent to give the desired amine (7 g), which was further recrystallized from MeOH/Et2O to give the title compound (5.4 g, 40%), mp>241° C. TLC (30% MeOH in CH2Cl2); Rf=0.33. IR (KBr) cm1, 3350-3000 (broad), 1675, 1625. was added under N2 at -10° C. was added dropwise After the addition an orange oil separated to warm A mixture of MeOH (60 ml) and glacial acetic acid (4.5 ml, 0.08M) was slowly added The solvents were evaporated in vacuo chromatographed on silica gel (EM-60) with 30% MeOH in CH2Cl2 as the eluent

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

Procedure: To a solution of lithium diisopropylamide (LDA), prepared from n-BuLi (106.6 ml, 0.16M) and diisopropylamine (16.7 g, 23.1 ml, 0.16M), in dry THF (100 ml) was added under N2 at -10° C., 5-methylisoxazole (6.8 g, 0.08M). The resultant yellow suspension was mechanically stirred at -10° C. for 30 min before the 4,5-dihydro-2-methylthiothiazole (11 g, 0.08M) was added dropwise. After the addition was complete, an orange oil separated, and the mixture was allowed to warm to ambient over a period of 20 hr. A mixture of MeOH (60 ml) and glacial acetic acid (4.5 ml, 0.08M) was slowly added and the resultant reddish solution was stirred at ambient overnight. The solvents were evaporated in vacuo, and the residual oil was flash column chromatographed on silica gel (EM-60) with 30% MeOH in CH2Cl2 as the eluent to give the desired amine (7 g), which was further recrystallized from MeOH/Et2O to give the title compound (5.4 g, 40%), mp>241° C. TLC (30% MeOH in CH2Cl2); Rf=0.33. IR (KBr) cm1, 3350-3000 (broad), 1675, 1625. was added under N2 at -10° C. was added dropwise After the addition an orange oil separated to warm A mixture of MeOH (60 ml) and glacial acetic acid (4.5 ml, 0.08M) was slowly added The solvents were evaporated in vacuo chromatographed on silica gel (EM-60) with 30% MeOH in CH2Cl2 as the eluent

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.6 g (5×10-2 mols) of 2-methylthiothiazoline and 12.0 g (6×10-2 mols) of 2-(2,5-diketopyrrolidyl)ethyl bromide were heated with stirring for about 3 hours on an oil bath which had been heated to a temperature of 130° C. Thereafter, the reaction system was allowed to cool to room temperature. 50 ml of acetone was added to the reaction system. The resulting precipitate was recovered by decantation. 11.1 g of the desired product was obtained in a 66% yield. to cool to room temperature The resulting precipitate was recovered by decantation