N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amine → 6-chloro-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

Beteiligte Stoffe

Reaktionsschritte

A 250-mL round-bottom flask was charged with 6-chloro-3-oxo-3,4-dihydro-2h-1-4-benzoxazine-7-sulfonyl chloride (Enamine, Kiev, Ukraine, 3.849 g, 13.64 mmol), N-(4-methoxybenzyl)thiazol-2-amine (3.61 g, 16.37 mmol), and THF (68.2 ml) to give a thick suspension. The flask was sonicated for 30 s, then cooled in a dry ice-acetone bath for 10 min. Lithium bis(trimethylsilyl)amide (1M in THF) (30.0 ml, 30.0 mmol) was added dropwise over 5 min. After another 5 min, the flask was transferred to an ice-bath. After 1 h of stirring, an additional portion of base solution (5 mL) was added. After 10 min, the mixture was diluted with saturated aq. ammonium chloride (150 mL) and water (50 mL). The mixture was extracted with EtOAc (3×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was concentrated from DCM (2×). The resulting solid was taken up in THF (100 mL) to give a thin suspension. The flask was cooled in an ice-bath for 5 min, then borane-tetrahydrofuran complex (1M in THF) (1.173 g, 13.64 mmol). Following the addition, the cooling bath was removed. After 2 h, borane-tetrahydrofuran complex (1M in THF) from another bottle (30 mL) was added. Some bubbling was observed, and the mixture lightened. After 16 h of stirring, the mixture was quenched by the careful addition of MeOH (20 mL). After 2 h, the mixture was concentrated, then concentrated from MeOH/DCM. The residual oil was treated with MeOH, and the resulting mixture was stirred for 5 h. The sides of the flask were scraped with a spatula, and the flask was cooled in an ice-bath for 10 min. The mixture was then filtered, and the collected solid was washed with ice-cold MeOH (2×), dried under a stream of N2 (g), then dried under vacuum to give 6-chloro-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (2.3249 g, 5.14 mmol, 37.7% yield) as a white solid: 1H NMR (400 MHz, DMSO-d6) δ=7.41 (d, J=3.5 Hz, 1 H), 7.30-7.19 (m, 5 H), 6.85 (d, J=8.7 Hz, 2 H), 6.68 (s, 1 H), 5.15 (s, 2 H), 4.12 (t, J=4.3 Hz, 2 H), 3.71 (s, 3 H), 3.37 (d, J=2.2 Hz, 2 H); m/z (ESI) 452.2 (M+H)+.

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