Triethylamine → HCID 59853592, compound

Participants

Reaction Conditions

Reaction Steps

Hydrazine monohydrate (20.1 mL, 414 mmol) was added to a solution of N-benzothiazol-6-yl-N-methyl-methanesulfonamide (Example 7b, 10.06 g, 41.5 mmol) in ethanol (150 mL) at 25° C. The reaction mixture was heated to 50° C. for 13 h, and then was concentrated in vacuo. The residue was dissolved in 1.0 M aqueous hydrochloric acid solution (100 mL) and the pH was adjusted to 7 by the addition of 6.0 M aqueous hydrochloric acid solution. The resulting mixture was extracted with ethyl acetate (2×150 mL) and the aqueous layer was acidified to pH 3 by the addition of 6.0 M aqueous hydrochloric acid solution, and then neutralized to pH 7 by the addition of solid sodium bicarbonate. The mixture was again extracted with ethyl acetate (1×150 mL) and all organic layers were combined, dried over sodium sulfate, filtered and concentrated in vacuo. The orange solid thus obtained was dissolved in tetrahydrofuran (150 mL) and triethylamine (12.3 mL, 88.2 mmol), and 4-chloro-3-oxo-butyric acid methyl ester (5.10 mL, 44.2 mmol) were added sequentially at 25° C. The reaction mixture was stirred at 25° C. for 2 h, and then was partitioned between 1.0 M aqueous hydrochloric acid solution (150 mL) and ethyl acetate (2×150 mL). The organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Purification of the residue by flash column chromatography (Merck silica gel 60, 40-63 μm, 20→100% ethyl acetate in hexanes) afforded the desired product, [7-(methanesulfonyl-methyl-amino)-4H-benzo[1,4]thiazin-3-yl]-acetic acid methyl ester (8.40 g, 25.6 mmol, 64% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ: 2.86 (3H, s), 3.27 (3H, s), 3.43 (2H, s), 3.72 (3H, s), 6.86 (1H, d, J=8.6 Hz), 7.12 (1H, dd, J1=2.3 Hz, J2=8.6 Hz), 7.21 (1H, d, J=2.4 Hz), 10.63 (1H, s).

Provenance & Evidence