1-Bromo-4-(methylsulphonyl)benzene → 6-chloro-N-(4-methylsulfonylphenyl)pyrazin-2-amine

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1-bromo-4-(methylsulfonyl)benzene (18.6 g, 79.12 mmol) then cesium carbonate (33.5 g, 102.85 mmol) were successively added to a solution of 6-chloropyrazin-2-amine (10.25 g, 79.12 mmol) in 1,4-dioxane (300 ml). The mixture was purged with nitrogen, then (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (2.75 g, 4.75 mmol) and diacetoxypalladium (0.533 g, 2.37 mmol) were added, the mixture was purged with nitrogen then heated to 85°C for 3 hours. After cooling the mixture was diluted with ethylacetate (300 mL), filtered, the solid washed with ethyl acetate (2x100 mL). Filtrate was washed with water (500 mL) => _emulsion, 100 mL of brine were added to help separation of layers._ Organics were washed with brine and dried over MgSO4. Crude product (28g) was purified by flash chromatography on silica gel (solid deposit) eluting with 1 to 4% methanolic ammonia (7 N) in dichloromethane => _no separation !! crude was flushed_. The solvent was evaporated to dryness to afford crude product (22g). It was recrystallised from EtOAc (~450 mL) to afford 6-chloro-N-(4-(methylsulfonyl)phenyl)pyrazin-2-amine (14.00 g, 62.4 %, EN03787-21-01) as a white crystalline solid => _purity = 91%, contains 6.9% EtOAc_. Silica (63-200 µm) was added to filtrate and it was concentrated to dryness to be purified by flash chromatography on silica gel eluting with 1 to 4% methanolic ammonia (7 N) in dichloromethane => _again, no separation !!_ Fractions containing product were combined and concentrated to dryness. Residue (4.3g) was recrystallised from EtOAc (~70 mL) to afford 6-chloro-N-(4-(methylsulfonyl)phenyl)pyrazin-2-amine (1.80 g, 8.0 %, EN03787-21-02) as a white crystalline solid => _purity = 91%, contains 6.5% EtOAc._ **_HMS03866_**

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