4-(methylsulfonylmethyl)aniline

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 solution of 1-[(methylsulphonyl)methyl]-4-nitrobenzene (4 g) in ethyl acetate (300 ml) containing a catalytic amount of palladium on carbon (10%, prehydrogenated, 0.5 g) was hydrogenated at room temperature and pressure until hydrogen uptake ceased (1400 ml, 1 h). The catalyst was filtered off and the filter cake washed with warm ethanol (2×80 ml). The filtrates were combined and concentrated under vacuum to afford the title compound (1.9 g) as a pale yellow crystalline solid, m.p. 167°-168° C. was hydrogenated at room temperature (1400 ml, 1 h) The catalyst was filtered off the filter cake washed with warm ethanol (2×80 ml) concentrated under vacuum

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 solution of Example 328b (3.80 g, 20.5 mmol) in N,N-dimethylformamide (103 mL) was added N-iodosuccinimide (5.08 g, 22.56 mmol). The reaction mixture was stirred at ambient temperature for 1 hour. The reaction mixture was quenched with 150 mL 10% aqueous sodium thiosulfate and 100 mL saturated aqueous sodium bicarbonate. The reaction mixture was extracted with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride and concentrated. Water was added, and the resulting suspension was stirred at ambient temperature 10 minutes. The suspension was filtered, and the solids collected was rinsed with water, and dried overnight to provide the title compound. The reaction mixture was quenched with 150 mL 10% aqueous sodium thiosulfate and 100 mL saturated aqueous sodium bicarbonate The reaction mixture was extracted with ethyl acetate The combined organic layers were washed with saturated aqueous sodium chloride concentrated Water was added the resulting suspension was stirred at ambient temperature 10 minutes The suspension was filtered the solids collected was rinsed with water dried overnight

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

Procedure: To a solution of Example 3b (1.12 g, 6.03 mmol) in dimethylformamide (60.3 mL) was added N-iodosuccinimide (1.49 g, 6.63 mmol). The reaction mixture was stirred at ambient temperature for 90 minutes. The reaction mixture was quenched with 10% sodium thiosulfate and saturated aqueous sodium bicarbonate, and extracted with ethyl acetate three times. The combined organic layers were washed with saturated aqueous sodium chloride, dried with anhydrous magnesium sulfate, filtered, and concentrated. Water was added to the residue, and the mixture was stirred at ambient temperature for 10 minutes and filtered to give the title compound (1.55 g, 83%). The reaction mixture was quenched with 10% sodium thiosulfate and saturated aqueous sodium bicarbonate extracted with ethyl acetate three times The combined organic layers were washed with saturated aqueous sodium chloride dried with anhydrous magnesium sulfate filtered concentrated Water was added to the residue the mixture was stirred at ambient temperature for 10 minutes filtered

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

Procedure: To a solution of Example 3b (1.12 g, 6.03 mmol) in dimethylformamide (60.3 mL) was added N-iodosuccinimide (1.49 g, 6.63 mmol). The reaction mixture was stirred at ambient temperature for 90 minutes. The reaction mixture was quenched with 10% sodium thiosulfate and saturated aqueous sodium bicarbonate, and extracted with ethyl acetate three times. The combined organic layers were washed with saturated aqueous sodium chloride, dried with anhydrous magnesium sulfate, filtered, and concentrated. Water was added to the residue, and the mixture was stirred at ambient temperature for 10 minutes and filtered to give the title compound (1.55 g, 83%). The reaction mixture was quenched with 10% sodium thiosulfate and saturated aqueous sodium bicarbonate extracted with ethyl acetate three times The combined organic layers were washed with saturated aqueous sodium chloride dried with anhydrous magnesium sulfate filtered concentrated Water was added to the residue the mixture was stirred at ambient temperature for 10 minutes filtered

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

Procedure: The title compound was prepared in 66% yield from 8-ethoxymethylene-6,8-dihydro-1-thia-3,6-diaza-as-indacen-7-one and 4-methylsulfonylmethylaniline according to Procedure J: 1H NMR (DMSO-d6): δ11.1 (d, 1H), 11.0 (s, 1H), 9.3 (s, 1H), 8.1 (d, 1H), 7.8 (d, 1H), 7.5 (q, 4H), 7.1 (d, 1H), 4.45 (s, 2H), 2.9 (s. 3H); APCI−MS m/z 384 (M−H)−.

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

Procedure: To a solution of Example 110B (1.117 g, 6.03 mmol) in dimethylformamide (60.3 mL) was added N-iodosuccinimide (1.492 g, 6.63 mmol). The reaction mixture was stirred at room temperature for 90 minutes. The reaction mixture was quenched with 10% sodium thiosulfate and saturated aqueous sodium bicarbonate and extracted with ethyl acetate three times. The combined organic layers were washed with saturated aqueous sodium chloride, dried with anhydrous magnesium sulfate, filtered, and concentrated. Water was added to the residue, and the mixture was stirred at room temperature for 10 minutes and filtered to give the title compound (1.55 g, 83%). The reaction mixture was quenched with 10% sodium thiosulfate and saturated aqueous sodium bicarbonate extracted with ethyl acetate three times The combined organic layers were washed with saturated aqueous sodium chloride dried with anhydrous magnesium sulfate filtered concentrated Water was added to the residue the mixture was stirred at room temperature for 10 minutes filtered

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

Procedure: A solution of 1-[(methylsulphonyl)methyl]-4-nitrobenzene (4 g) in ethyl acetate (300 ml) containing a catalytic amount of palladium on carbon (10%, prehydrogenated, 0.5 g) was hydrogenated at room temperature and pressure until hydrogen uptake ceased (1400 ml, 1 h). The catalyst was filtered off and the filter cake washed with warm ethanol (2×80 ml). The filtrates were combined and concentrated under vacuum to afford the title compound (1.9 g) as a pale yellow crystalline solid, m.p. 167°-168° C. was hydrogenated at room temperature (1400 ml, 1 h) The catalyst was filtered off the filter cake washed with warm ethanol (2×80 ml) concentrated under vacuum

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

Procedure: According to the general procedure for synthesis of 1-(4-(4-(cyclobutylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)phenylsulfonyl)piperidin-4-ol, 4-(methylsulfonylmethyl)aniline and 2-Chloro-N-cylclobutyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine gave N4-cyclobutyl-N2-(4-methylsulfonylmethyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2,4-diamine (MS calcd for C18H21N5O2S 371.5, found [MH] 372.1; UV 205.1, 273.6, 304.5 nm).