N-(4-bromophenyl)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:

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

Procedure: From bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine (81 mg) and mesyl-(4-bromo-phenyl)-carbamic acid tert-butyl ester (prepared from N-(4-bromo-phenyl)-methane sulfonamide and di-t butyl carbonate in acetonitrile in the presence of DMAP, 105 mg) instead of 4-bromobenzoic acid methyl ester in Example 1-D-08, in the same manner as Example 1-D-08, a crude product of mesyl-[4-(4-{2-[bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidin-7-yl)-phenyl]-carbamic acid tert-butyl ester was obtained, and then the PMB groups were removed according to Deprotection method 1, to obtain the desired compound (D-44) as a pale yellow powder (12 mg, 10%).

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

Procedure: From bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine (81 mg) and mesyl-(4-bromo-phenyl)-carbamic acid tert-butyl ester (prepared from N-(4-bromo-phenyl)-methane sulfonamide and di-t butyl carbonate in acetonitrile in the presence of DMAP, 105 mg) instead of 4-bromobenzoic acid methyl ester in Example 1-D-08, in the same manner as Example 1-D-08, a crude product of mesyl-[4-(4-{2-[bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidin-7-yl)-phenyl]-carbamic acid tert-butyl ester was obtained, and then the PMB groups were removed according to Deprotection method 1, to obtain the desired compound (D-44) as a pale yellow powder (12 mg, 10%).

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

Procedure: Methyl iodide (2.38 g, 0.0382M) was added to a mixture of N-(4-bromophenyl)methanesulfonamide (6.37 g, 0.0255M) and potassium carbonate (5.21 g, 0.0382M) in dimethylformamide (50 ml) at room temperature under an atmosphere of nitrogen. The reaction mixture was stirred for a further 24 hrs after which time it was partitioned between diethylether (100 ml) and water (100 ml). The aqueous was extracted further with diethyl ether (2×100 ml). The combined organics were dried over magnesium sulfate, filtered and the solvent concentrated in vacuuo to afford the title compound as a white solid (5.6 g). was partitioned between diethylether (100 ml) and water (100 ml) The aqueous was extracted further with diethyl ether (2×100 ml) The combined organics were dried over magnesium sulfate filtered the solvent concentrated in vacuuo

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

Procedure: Methane sulfonyl chloride (2.4 ml, 0.031 M) was added to a solution of 4-bromo-aniline (5.28 g, 0.031 M) and pyridine (2.5 ml, 0.031 M) in dichloromethane (100 ml) at 0° C. The reaction mixture was stirred for 1 hr, after which time it was partitioned between dichloromethane (100 ml) and 1N hydrochloric acid (100 ml). The organics were separated and dried over magnesium sulfate, filtered and concentrated in vacuuo to afford the title compound as a white solid (6.37 g). after which time it was partitioned between dichloromethane (100 ml) and 1N hydrochloric acid (100 ml) The organics were separated dried over magnesium sulfate filtered concentrated in vacuuo

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

Procedure: Methane sulfonyl chloride (2.4 ml, 0.031 M) was added to a solution of 4-bromo-aniline (5.28 g, 0.031 M) and pyridine (2.5 ml, 0.031 M) in dichloromethane (100 ml) at 0° C. The reaction mixture was stirred for 1 hr, after which time it was partitioned between dichloromethane (100 ml) and 1N hydrochloric acid (100 ml). The organics were separated and dried over magnesium sulfate, filtered and concentrated in vacuuo to afford the title compound as a white solid (6.37 g). after which time it was partitioned between dichloromethane (100 ml) and 1N hydrochloric acid (100 ml) The organics were separated dried over magnesium sulfate filtered concentrated in vacuuo

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

Procedure: A solution of N-(4-bromophenyl)methanesulfonamide (200 mg, 0.80 mmol), potassium carbonate (2 eq) and methyl iodide (2 eq) in DMF (2 mL) was heated at 60° C. for 18 h. After cooling to rt the mixture was diluted with EtOAc and washed with water. The organic phase was collected, dried (MgSO4) and concentrated in vacuo to give N-(4-bromophenyl)-N-methylmethanesulfonamide. washed with water The organic phase was collected dried (MgSO4) concentrated in vacuo

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

Procedure: A solution of N-(4-bromophenyl)methanesulfonamide (200 mg, 0.80 mmol), potassium carbonate (2 eq) and methyl iodide (2 eq) in DMF (2 mL) was heated at 60° C. for 18 h. After cooling to rt the mixture was diluted with EtOAc and washed with water. The organic phase was collected, dried (MgSO4) and concentrated in vacuo to give N-(4-bromophenyl)-N-methylmethanesulfonamide. washed with water The organic phase was collected dried (MgSO4) concentrated in vacuo

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

Procedure: A solution of 4-bromoaniline (1.00 g, 5.81 mmol) and methanesulfonyl chloride (1 eq) in dichloromethane (10 mL) and pyridine (5 mL) was stirred at rt for 18 h. The resultant mixture was then diluted with dichloromethane and washed with water and then brine. The organic phase was collected, dried (MgSO4) and concentrated in vacuo to give N-(4-bromophenyl)methanesulfonamide. washed with water The organic phase was collected dried (MgSO4) concentrated in vacuo

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