N-[(4-aminophenyl)methyl]methanesulfonamide

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 sodium nitrite (0.3 g) in water (3 ml) was added, over 15 min. to a stirred suspension of N-[(4-aminophenyl)methyl]methanesulphonamide (0.7 g ) in concentrated hydrochloric acid (3 ml) and water (4 ml) keeping the temperature below 0°. After 1 h, the resulting suspension was added, over 1 min. to a stirred, ice-cooled solution of sodium acetate (3.2 g) and sodium sulphite (1.8 g) in water (20 ml) containing ice (5 g). The orange mixture was stirred for a further 30 min. then at room temperature for 1.5 h, and then warmed on the steam bath for 20 min. The mixture was cooled, concentrated hydrochloric acid (15 ml) added and the mixture warmed on the steam bath for 0.5 h. The solvent was evaporated in vacuo and the residue re-evaporated with absolute ethanol (2×50 ml). The residue was extracted with absolute ethanol (50 ml). The extract was evaporated in vacuo and the residue re-evaporated with ethanol (20 ml) to leave a brown oil, which partially crystallised after standing overnight. Ethanol (1 ml) was added and the title compound filtered off as light tan crystals (0.1 g) m.p. 165°-70° (dec.) the temperature below 0° the resulting suspension was added, over 1 min. to a stirred, ice- at room temperature for 1.5 h warmed on the steam bath for 20 min The mixture was cooled the mixture warmed on the steam bath for 0.5 h The solvent was evaporated in vacuo the residue re-evaporated with absolute ethanol (2×50 ml) The residue was extracted with absolute ethanol (50 ml) The extract was evaporated in vacuo the residue re-evaporated with ethanol (20 ml) to leave a brown oil, which partially crystallised after standing overnight Ethanol (1 ml) was added the title compound filtered off as light tan crystals (0.1 g) m.p. 165°-70° (dec.)

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

Procedure: A solution of sodium nitrite (0.3 g) in water (3 ml) was added, over 15 min. to a stirred suspension of N-[(4-aminophenyl)methyl]methanesulphonamide (0.7 g ) in concentrated hydrochloric acid (3 ml) and water (4 ml) keeping the temperature below 0°. After 1 h, the resulting suspension was added, over 1 min. to a stirred, ice-cooled solution of sodium acetate (3.2 g) and sodium sulphite (1.8 g) in water (20 ml) containing ice (5 g). The orange mixture was stirred for a further 30 min. then at room temperature for 1.5 h, and then warmed on the steam bath for 20 min. The mixture was cooled, concentrated hydrochloric acid (15 ml) added and the mixture warmed on the steam bath for 0.5 h. The solvent was evaporated in vacuo and the residue re-evaporated with absolute ethanol (2×50 ml). The residue was extracted with absolute ethanol (50 ml). The extract was evaporated in vacuo and the residue re-evaporated with ethanol (20 ml) to leave a brown oil, which partially crystallised after standing overnight. Ethanol (1 ml) was added and the title compound filtered off as light tan crystals (0.1 g) m.p. 165°-70° (dec.) the temperature below 0° the resulting suspension was added, over 1 min. to a stirred, ice- at room temperature for 1.5 h warmed on the steam bath for 20 min The mixture was cooled the mixture warmed on the steam bath for 0.5 h The solvent was evaporated in vacuo the residue re-evaporated with absolute ethanol (2×50 ml) The residue was extracted with absolute ethanol (50 ml) The extract was evaporated in vacuo the residue re-evaporated with ethanol (20 ml) to leave a brown oil, which partially crystallised after standing overnight Ethanol (1 ml) was added the title compound filtered off as light tan crystals (0.1 g) m.p. 165°-70° (dec.)

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

Procedure: A solution of N-[(4-nitrophenyl)methyl]methanesulphonamide (2.5 g) in a mixture of ethanol (90 ml) and ethyl acetate (90 ml) was hydrogenated at room temperature and pressure over palladium oxide on charcoal (10%; 50% paste with water, 1 g) until uptake of hydrogen ceased (15 min., 820 ml). was hydrogenated at room temperature (15 min., 820 ml)

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

Procedure: 5.309 g N-(4-Amino-benzyl)-methanesulfonamide (obtained in Step 2, 26.5 mmol) and 4.739 g 4,6-dichloropyrimidine (31.81 mmol) was dissolved in 120 cm3 of isopropyl-alcohol, 6.93 cm3 N,N-diisopropyl-ethylamine (5.140 g, 39.76 mmol) was added and the mixture was refluxed for four days. The reaction mixture was cooled to room temperature and the precipitated compound was filtered off. The light yellow product was washed well with diethyl-ether and air-dried. 3.813 g N-[4-(6-Chloro-pyrimidin-4-ylamino)-benzyl]-methanesulfonamide was obtained above 98% purity in 46% overall yield. For analitical results and compound identification see Table 1. The compound was used as a starting material in the preparation of Example 34-58 and 76. the mixture was refluxed for four days the precipitated compound was filtered off The light yellow product was washed well with diethyl-ether air-dried

Conditions: temp:-55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 18.0 g (89.9 mmol, 1.0 equiv.) of N-[(4-aminophenyl)methyl]methanesulfonamide in 85 ml of water and 175 mL of concentrated aqueous hydrochloric acid at 0° C. was added a solution of 6.21 g (89.9 mmol, 1.0 equiv.) of sodium nitrite in 85 mL of water. The reaction mixture was stirred for fifteen minutes. Meanwhile a solution of 101.6 g of stannous chloride dihydrate in 175 mL of concentrated aqueous hydrochloric acid was prepared and cooled to -55° C. The solution of the diazonium salt was filtered into the stannous chloride solution. The reaction was maintained between -55° C. and -35° C. for one hour. The crystalline material was collected by filtration and dried under high vacuum at 65° C. for 16 hours to yield 23.9 g (>100%) of crude N-[(4-hydrazinylphenyl)methyl]methanesulfonamide hydrochloride. The solution of the diazonium salt was filtered into the stannous chloride solution The reaction was maintained between -55° C. and -35° C. for one hour The crystalline material was collected by filtration dried under high vacuum at 65° C. for 16 hours

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

Procedure: To a suspension of 25.9 g (113 mmol, 1.0 equiv.) of N-[(4-nitrophenyl)methyl]methanesulfonamide in 113 mL of 1N HCl (113 mmol, 1.0 equiv.), 113 mL of water and 225 mL of ethanol was added 5.18 g of 10% palladium on carbon. This mixture was hydrogenated in a Parr apparatus at 60 psi for sixteen hours. The mixture was filtered through Celite. The ethanol was removed in vacuo and the pH adjusted to 9, at which point the product had precipitated. The precipitate was isolated by filtration and dried in vacuo to yield 18.0 g (80%) of N-[(4-aminophenyl)methyl]-methanesulfonamide. This mixture was hydrogenated in a Parr apparatus at 60 psi for sixteen hours The mixture was filtered through Celite The ethanol was removed in vacuo had precipitated The precipitate was isolated by filtration dried in vacuo

Conditions: temp:-55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 18.0 g (89.9 mmol, 1.0 equiv.) of N-[(4-aminophenyl)methyl]methanesulfonamide in 85 ml of water and 175 mL of concentrated aqueous hydrochloric acid at 0° C. was added a solution of 6.21 g (89.9 mmol, 1.0 equiv.) of sodium nitrite in 85 mL of water. The reaction mixture was stirred for fifteen minutes. Meanwhile a solution of 101.6 g of stannous chloride dihydrate in 175 mL of concentrated aqueous hydrochloric acid was prepared and cooled to -55° C. The solution of the diazonium salt was filtered into the stannous chloride solution. The reaction was maintained between -55° C. and -35° C. for one hour. The crystalline material was collected by filtration and dried under high vacuum at 65° C. for 16 hours to yield 23.9 g (>100%) of crude N-[(4-hydrazinylphenyl)methyl]methanesulfonamide hydrochloride. The solution of the diazonium salt was filtered into the stannous chloride solution The reaction was maintained between -55° C. and -35° C. for one hour The crystalline material was collected by filtration dried under high vacuum at 65° C. for 16 hours

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

Procedure: N-(4-Aminobenzyl)methanesulfonamide (352 mg, 1.76 mmol) was dissolved in acetonitrile (3 mL) and tetrahydrofuran (4 mL). The reaction mixture was added pyridine (0.17 mL, 2.11 mmol) and phenyl chloroformate (0.23 mL, 1.85 mmol) and stirred at room temperature for 3 h under nitrogen atmosphere. TLC showed complete consumption of starting material. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic part was washed with water and brine. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The crude was purified by column chromatography to give phenyl 4-(methylsulfonamidomethyl)phenylcarbamate (438 mg, 78%). consumption of starting material The reaction mixture was diluted with water extracted with ethyl acetate The organic part was washed with water and brine The organic layer was dried over magnesium sulfate concentrated under reduced pressure The crude was purified by column chromatography

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

Procedure: N-(4-Nitrobenzyl)methanesulfonamide (881 mg, 3.83 mmol) was dissolved in methanol/tetrahydrofuran (1:1, 35 mL). 10% Pd/C (264 mg, 3 eq) was added to it. The resulting mixture was stirred at room temperature for overnight under H2. TLC showed complete consumption of starting material. The mixture was filtered through celite bed and the filterate was concentrated under reduced pressure. The crude was purified by column chromatography to give N-(4-aminobenzyl)methanesulfonamide (352 mg, 46%). consumption of starting material The mixture was filtered through celite bed the filterate was concentrated under reduced pressure The crude was purified by column chromatography

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

Procedure: A solution of sodium nitrite (0.3 g) in water (3 ml) was added, over 15 min. to a stirred suspension of N-[(4-aminophenyl)methyl]methanesulphonamide (0.7 g ) in concentrated hydrochloric acid (3 ml) and water (4 ml) keeping the temperature below 0°. After 1 h, the resulting suspension was added, over 1 min. to a stirred, ice-cooled solution of sodium acetate (3.2 g) and sodium sulphite (1.8 g) in water (20 ml) containing ice (5 g). The orange mixture was stirred for a further 30 min. then at room temperature for 1.5 h, and then warmed on the steam bath for 20 min. The mixture was cooled, concentrated hydrochloric acid (15 ml) added and the mixture warmed on the steam bath for 0.5 h. The solvent was evaporated in vacuo and the residue re-evaporated with absolute ethanol (2×50 ml). The residue was extracted with absolute ethanol (50 ml). The extract was evaporated in vacuo and the residue re-evaporated with ethanol (20 ml) to leave a brown oil, which partially crystallised after standing overnight. Ethanol (1 ml) was added and the title compound filtered off as light tan crystals (0.1 g) m.p. 165°-70° (dec.) the temperature below 0° the resulting suspension was added, over 1 min. to a stirred, ice- at room temperature for 1.5 h warmed on the steam bath for 20 min The mixture was cooled the mixture warmed on the steam bath for 0.5 h The solvent was evaporated in vacuo the residue re-evaporated with absolute ethanol (2×50 ml) The residue was extracted with absolute ethanol (50 ml) The extract was evaporated in vacuo the residue re-evaporated with ethanol (20 ml) to leave a brown oil, which partially crystallised after standing overnight Ethanol (1 ml) was added the title compound filtered off as light tan crystals (0.1 g) m.p. 165°-70° (dec.)