4-Methylmorpholine → (1R,2S)-2-{(3-chloro-4-fluoro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclopentanecarboxylic acid methyl ester

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Reaction Steps

(1R,2S)-2-(3-Chloro-4-fluoro-benzylamino)-cyclopentanecarboxylic acid methyl ester (0.12 g, 0.42 mmol) was dissolved in anhydrous N,N-dimethylformamide (4.2 mL). (7-Methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (prepared as described in Example 1j, 0.154 g, 0.46 mmol) was added followed by N-methylmorpholine (0.101 mL, 0.92 mmol). The mixture was stirred until everything dissolved, approximately 5 min. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.088 g, 0.46 mmol) was added portionwise and the mixture was stirred at 25° C. for 15 h. The reaction mixture was quenched by pouring into 1.0 M aqueous hydrochloric acid solution (100 mL) and extracted with ethyl acetate (200 mL). The organic layer was concentrated in vacuo to afford the crude product, (1R,2S)-2-{(3-chloro-4-fluoro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclopentanecarboxylic acid methyl ester, which was used directly in the next step without further purification. LC-MS (ESI) calcd for C24H26ClFN4O7S2 600.09, found 601.1 [M+H+].

Provenance & Evidence