4-bromo-1-isocyanato-2-methylbenzene

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: Tetrahydro-1-(5-methylsulfinyl-1,3,4-thiadiazol-2-yl)-3-propargyl-6-hydroxy-2(1H)-pyrimidinone (0.05 mole) and 2-methyl-4-bromophenyl isocyanate (3.5 ml; 0.06 mole) are charged into a glass reaction vessel equipped with a mechanical stirrer. The mixture is stirred and triethylamine (1 drop) is added thereto. After the addition is completed the reaction mixture is allowed to stand for a period of about 1 hour. The mixture is then washed with hexane and is dried to yield the desired product tetrahydro-1-(5-methylsulfinyl-1,3,4-thiadiazol-2-yl)-3-propargyl-6-[N-(2-methyl-4-bromophenyl)carbamoyloxy]-2(1H)-pyrimidinone. equipped with a mechanical stirrer After the addition The mixture is then washed with hexane is dried

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

Procedure: Tetrahydro-1-(5-methylsulfinyl-1,3,4-thiadiazol-2-yl)-3-propargyl-6-hydroxy-2(1H)-pyrimidinone (0.05 mole) and 2-methyl-4-bromophenyl isocyanate (3.5 ml; 0.06 mole) are charged into a glass reaction vessel equipped with a mechanical stirrer. The mixture is stirred and triethylamine (1 drop) is added thereto. After the addition is completed the reaction mixture is allowed to stand for a period of about 1 hour. The mixture is then washed with hexane and is dried to yield the desired product tetrahydro-1-(5-methylsulfinyl-1,3,4-thiadiazol-2-yl)-3-propargyl-6-[N-(2-methyl-4-bromophenyl)carbamoyloxy]-2(1H)-pyrimidinone. equipped with a mechanical stirrer After the addition The mixture is then washed with hexane is dried

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

Procedure: A mixture of 9.22 grams (0.04 mole) of 4-bromo-2-methylphenyl isocyanate, 5.78 grams (0.04 mole) of ethyl nitroacetate, 6.01 grams (0.04 mole) of anhydrous potassium carbonate and 90 milliliters of benzene was stirred and heated under reflux for 3 hours then cooled and stirred at room temperature for a period of about 16 hours. The precipitated material was filtered off and thoroughly triturated with 200 milliliters of ice water, filtering to remove a precipitate which was discarded. Chilling and acidification of the filtrate with concentrated HCl caused precipitation of a yellow-white solid which was collected, water-washed and air-dried. Recrystallization from benzene-cyclohexane (3:1) gave 3.38 grams (0.01 mole) of ethyl 3-[(4-bromo-2-methylphenyl)amino]-2-nitro-3-oxopropanoate as white crystals having a melting point of 126° C.-129° C. heated under reflux for 3 hours then cooled stirred at room temperature for a period of about 16 hours The precipitated material was filtered off thoroughly triturated with 200 milliliters of ice water filtering to remove a precipitate which Chilling precipitation of a yellow-white solid which was collected water-washed air-dried Recrystallization from benzene-cyclohexane (3:1)

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

Procedure: A mixture of 9.22 grams (0.04 mole) of 4-bromo-2-methylphenyl isocyanate, 5.78 grams (0.04 mole) of ethyl nitroacetate, 6.01 grams (0.04 mole) of anhydrous potassium carbonate and 90 milliliters of benzene was stirred and heated under reflux for 3 hours then cooled and stirred at room temperature for a period of about 16 hours. The precipitated material was filtered off and thoroughly triturated with 200 milliliters of ice water, filtering to remove a precipitate which was discarded. Chilling and acidification of the filtrate with concentrated HCl caused precipitation of a yellow-white solid which was collected, water-washed and air-dried. Recrystallization from benzene-cyclohexane (3:1) gave 3.38 grams (0.01 mole) of ethyl 3-[(4-bromo-2-methylphenyl)amino]-2-nitro-3-oxopropanoate as white crystals having a melting point of 126° C.-129° C. heated under reflux for 3 hours then cooled stirred at room temperature for a period of about 16 hours The precipitated material was filtered off thoroughly triturated with 200 milliliters of ice water filtering to remove a precipitate which Chilling precipitation of a yellow-white solid which was collected water-washed air-dried Recrystallization from benzene-cyclohexane (3:1)

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

Procedure: To a solution of 2-[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetohydrazide (800 mg, 3.79 mmol) in dry dichloromethane (5 mL) was added 4-bromo-1-isocyanato-2-methylbenzene (803 mg, 3.79 mmol). The reaction was allowed to progress for 1 h at room temperature (became a thick suspension that could not be stirred). The reaction mixture was diluted with dichloromethane (10 mL) and the precipitate was collected by filtration. A second crop was obtained by filtration and the two crops were combined, rinsed with minimal dichloromethane and dried to constant weight under high vacuum to provide the title product (1.54 g, 3.64 mmol, 96% yield) as a white solid. MS(ES)+ m/e 422.9 [M+H]+. This material was 76% pure by LCMS (UV214) and was used as is in the next step. the precipitate was collected by filtration A second crop was obtained by filtration rinsed with minimal dichloromethane dried to constant weight under high vacuum

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

Procedure: A mixture of 9.22 grams (0.04 mole) of 4-bromo-2-methylphenyl isocyanate, 5.78 grams (0.04 mole) of ethyl nitroacetate, 6.01 grams (0.04 mole) of anhydrous potassium carbonate and 90 milliliters of benzene was stirred and heated under reflux for 3 hours then cooled and stirred at room temperature for a period of about 16 hours. The precipitated material was filtered off and thoroughly triturated with 200 milliliters of ice water, filtering to remove a precipitate which was discarded. Chilling and acidification of the filtrate with concentrated HCl caused precipitation of a yellow-white solid which was collected, water-washed and air-dried. Recrystallization from benzene-cyclohexane (3:1) gave 3.38 grams (0.01 mole) of ethyl 3-[(4-bromo-2-methylphenyl)amino]-2-nitro-3-oxopropanoate as white crystals having a melting point of 126° C.-129° C. Elemental analysis of the product indicated the following: heated under reflux for 3 hours then cooled stirred at room temperature for a period of about 16 hours The precipitated material was filtered off thoroughly triturated with 200 milliliters of ice water filtering to remove a precipitate which Chilling precipitation of a yellow-white solid which was collected water-washed air-dried Recrystallization from benzene-cyclohexane (3:1)

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

Procedure: A mixture of 9.22 grams (0.04 mole) of 4-bromo-2-methylphenyl isocyanate, 5.78 grams (0.04 mole) of ethyl nitroacetate, 6.01 grams (0.04 mole) of anhydrous potassium carbonate and 90 milliliters of benzene was stirred and heated under reflux for 3 hours then cooled and stirred at room temperature for a period of about 16 hours. The precipitated material was filtered off and thoroughly triturated with 200 milliliters of ice water, filtering to remove a precipitate which was discarded. Chilling and acidification of the filtrate with concentrated HCl caused precipitation of a yellow-white solid which was collected, water-washed and air-dried. Recrystallization from benzene-cyclohexane (3:1) gave 3.38 grams (0.01 mole) of ethyl 3-[(4-bromo-2-methylphenyl)amino]-2-nitro-3-oxopropanoate as white crystals having a melting point of 126° C.-129° C. Elemental analysis of the product indicated the following: heated under reflux for 3 hours then cooled stirred at room temperature for a period of about 16 hours The precipitated material was filtered off thoroughly triturated with 200 milliliters of ice water filtering to remove a precipitate which Chilling precipitation of a yellow-white solid which was collected water-washed air-dried Recrystallization from benzene-cyclohexane (3:1)

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