1-isothiocyanato-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:; See reaction.notes.procedure_details.

Procedure: A mixture of ethyl 4-amino-3-hydroxy-phenylacetate (3.3 g, Reference Example 2) and o-tolylisothiocyanate (2.5 mL) in ethanol (150 mL) was stirred at room temperature for about 2 hours. After standing at room temperature overnight the mixture was evaporated and the residue was subjected to flash chromatography on silica eluting with a mixture of pentane and ethyl acetate (7:3, v/v) to give a yellow foam. A solution of this material in ethanol (150 mL was treated with dicyclohexylcarbodiimide (3.0 g) and the mixture was heated at reflux temperature for 2 hours. The mixture was evaporated and the residue subjected to short column chromatography on silica eluting with a mixture of 5-10% tert-butyl methyl ether in dichloromethane to remove dicyclohexylurea. The resulting light yellow oil was dissolved in ethanol (100 mL) and the solution was treated with sodium hydroxide solution (15 mL, 1M) then heated at reflux temperature for 2 hours. The reaction mixture was evaporated and the residue was dissolved in water. The solution was washed with ethyl acetate and the aqueous layer was acidified to pH 1 by addition of concentrated hydrochloric acid. The resulting white precipitate was collected by filtration, then washed thoroughly with water, and then dried to give the title compound (1.8 g) as a white solid. After standing at room temperature overnight the mixture was evaporated the residue was subjected to flash chromatography on silica eluting with a mixture of pentane and ethyl acetate (7:3 v/v) to give a yellow foam the mixture was heated at reflux temperature for 2 hours The mixture was evaporated the residue subjected to short column chromatography on silica eluting with a mixture of 5-10% tert-butyl methyl ether in dichloromethane to remove dicyclohexylurea The resulting light yellow oil was dissolved in ethanol (100 mL) the solution was treated with sodium hydroxide solution (15 mL, 1M) then heated at reflux temperature for 2 hours The reaction mixture was evaporated the residue was dissolved in water The solution was washed with ethyl acetate the aqueous layer was acidified to pH 1 by addition of concentrated hydrochloric acid The resulting white precipitate was collected by filtration washed thoroughly with water dried

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

Procedure: The compound of example 272 was prepared analogous to compound of example 256 by reaction of compound of example 223 with 2-methyl phenyl isothiocyanate. The compound of example 272 was used directly without isolation, for the preparation of compound of example 273.

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

Procedure: The compound of example 71 was prepared analogous to compound of example 51 by reaction of compound of example 6 with 2-methyl phenyl isothiocyanate. The compound of example 71 was used directly without isolation for the preparation of compound of example 72.

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

Procedure: The tide compound was prepared by the procedure described in Example 7 using 9.2 g of N-ethyl glycine, 7.4 g of 2-tolyl-isothiocyanate, 10.1 g of triethylamine, and 150 mL of methylene chloride. Purification was achieved through crystallization from ethanol. Title compound (3.6 g) was obtained as a creamy solid, m.p. 105°-108° C. Anal. Calcd. for. C12H14N2O S: C, 61.51; H, 6.02; N, 11.93. Found: C, 61.22; H, 5.96; N, 11.89. Mass spectrum (EI, M.+) m/z 234. The tide compound was prepared by the procedure Purification was achieved through crystallization from ethanol

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

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

Procedure: By using 5-(4-aminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione (150 mg, 0.473 mmol), and o-tolyl isothiocyanate (159 μL, 1.183 mmol), the title compound (66 mg, yield 30%) was obtained in the same manner as that of Example 24.

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of ethyl 3-(4-amino-3-hydroxyphenyl)-propionate (1.94 g) in ethanol (50 ml) was treated with o-tolyl isothiocyanate (1.66 g) and then heated at 40° C. for 2 hours. The mixture was evaporated then treated with ethanol (50 ml), then with diisopropylcarbodiimide (3 mL) and then stirred at 40° C. for 1 hour. The mixture was evaporated and the residue was treated with diethyl ether (50 ml) then filtered. The filtrate was evaporated to dryness and the residue subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane (2:3, v/v) to give the title compound (1.6 g) as a colourless oil. The mixture was evaporated then treated with ethanol (50 ml) The mixture was evaporated the residue was treated with diethyl ether (50 ml) then filtered The filtrate was evaporated to dryness the residue subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane (2:3

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of ethyl 3-(4-amino-3-hydroxyphenyl)-propionate (1.94 g) in ethanol (50 ml) was treated with o-tolyl isothiocyanate (1.66 g) and then heated at 40° C. for 2 hours. The mixture was evaporated then treated with ethanol (50 ml), then with diisopropylcarbodiimide (3 mL) and then stirred at 40° C. for 1 hour. The mixture was evaporated and the residue was treated with diethyl ether (50 ml) then filtered. The filtrate was evaporated to dryness and the residue subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane (2:3, v/v) to give the title compound (1.6 g) as a colourless oil. The mixture was evaporated then treated with ethanol (50 ml) The mixture was evaporated the residue was treated with diethyl ether (50 ml) then filtered The filtrate was evaporated to dryness the residue subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane (2:3

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

Procedure: To a DMF solution (2 ml) of ice-cooled bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine (80.0 mg, 0.148 mmol), 60% oily NaH (18 mg) was added, followed by stirring at room temperature for 30 minutes. To the reaction mixture, o-tolyl isothiocyanate (59.8 μl, 0.445 mmol) was added, followed by further stirring for 2 hours. The reaction mixture was ice-cooled, and quenched with water (1 ml). This was diluted with dichloromethane (10 ml), and washed with water (10 ml×2). After the organic layer was dried over sodium sulfate, the sodium sulfate was filtered off, and the filtrate was concentrated under reduced pressure, to obtain a crude product of 4-{2-[bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidine-7-carbothioic acid o-tolylamide as a brown solid (134 mg). The PMB groups were removed according to the above Deprotection method 3, to obtain the desired compound (D-210) as a yellow powder (35.9 mg, 54%). was added by further stirring for 2 hours cooled quenched with water (1 ml) This was diluted with dichloromethane (10 ml) washed with water (10 ml×2) After the organic layer was dried over sodium sulfate the sodium sulfate was filtered off the filtrate was concentrated under reduced pressure