Benzenemethanesulfonamide, 3-cyano-N-methyl- synthesis

Yield:933989-11-8 69%

Reaction Conditions:

Stage #1: m-(bromomethyl)benzonitrilewith sodium sulfite in ethanol;water; for 4 h;Heating / reflux;
Stage #2: with oxalyl dichloride;N,N-dimethyl-formamide in dichloromethane at 0 - 20; for 3 h;
Stage #3: methylamine in tetrahydrofuran; for 12 h;

Steps:

70.1

Example 70; 2-(3-Fluoro-phenylV4-methyl-pyrimidine-5-carboxylic acid 3-methylsulfamoylmethyl-benzylamide; Step 1; A solution of 3-bromomethyl-benzonitrile (2 g, 10.2 mmol) in EtOH (50 mL) is treated with a solution of Na₂SOs (1.3 g, 10.3 mmol) in H₂O (50 mL) and heated at reflux for 4 hours. The mixture is concentrated in vacuo. The residue is suspended in DCM (100 mL) and DMF (1 mL), cooled to O⁰C and treated with oxalyl chloride (8 mL, 43.4 mmol). The mixture is warmed to room temperature and stirred for 3 hours. The mixture is diluted with brine, extracted with DCM (2x100 mL), dried with Na₂SO^ filtered, and concentrated in vacuo. The residue is dissolved in THF (25 mL), methylamine (2 EPO M₃ 12.5 mL, 25 mmol) is added and the misture is stirred for 12 hours. The mixture is diluted with EtOAc (100 mL), washed with saturated aqueous NEJ₄Cl (2x100 mL), dried with Na₂SO₄, filtered, and concentrated in vacuo. The residue is purified by flash chromatography eluting with 20%-80% EtOAc/heptane to afford C-(3-cyano-phenylVN-methyl-methanesulfonamide (1.5 g, 69%) as a powder. MS: 209 (M+H); ¹H νMR (300 MHz, DMSO-d₆): δ 2.60 (d, J= 4.8 Hz, 3H), 4.44 (s, 2H), 7.02 (m, IH), 7.61 (m, IH), 7.74 (m, IH), 7.85 (m, 2H).

References:

WO2007/41634,2007,A1 Location in patent:Page/Page column 62-63