Reaktion #818523

Reaktionsgleichung

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

(7-Methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid

Ethyl 2-(2,2-dimethylhydrazinyl)cyclopentanecarboxylate

N-methylmorpholine

→

cis-N-[3-(1-dimethylamino-4-hydroxy-2-oxo-2,4a,5,6,7,7a-hexahydro-1H-[1]pyrindin-3-yl)-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl]-methanesulfonamide hydrochloride

Ausbeute 52.4%

Lösungsmittel

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.DISSOLUTIONdissolved, approximately 5 min
2. 2
   workup.STIRRINGthe mixture was stirred at 25° C. for 16 h
3. 3
   SonstigeThe reaction was quenched via addition of saturated aqueous sodium bicarbonate solution (20 mL)
4. 4
   ExtraktionThe mixture was extracted with ethyl acetate (3×30 mL)
5. 5
   Waschenwashed with saturated aqueous brine solution (20 mL)
6. 6
   TrocknenThe resulting solution was dried over magnesium sulfate
7. 7
   Filtrationfiltered
8. 8
   Einengenconcentrated in vacuo
9. 9
   Sonstigeto afford a golden oil
10. 10
    SonstigeThe residue was triturated with ethyl acetate

Vorschrift

Ethyl 2-(2,2-dimethylhydrazinyl)cyclopentanecarboxylate (0.16 g, 0.82 mmol) was dissolved in anhydrous N,N-dimethylformamide (8 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, 0.27 g, 0.82 mmol) was added followed by N-methylmorpholine (0.19 mL, 1.72 mmol). The mixture was stirred until everything dissolved, approximately 5 min. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.16 g, 0.86 mmol) was added and the mixture was stirred at 25° C. for 16 h. The reaction was quenched via addition of saturated aqueous sodium bicarbonate solution (20 mL). The mixture was extracted with ethyl acetate (3×30 mL). The organic layers were combined and washed with saturated aqueous brine solution (20 mL). The resulting solution was dried over magnesium sulfate, filtered, and concentrated in vacuo to afford a golden oil. The residue was triturated with ethyl acetate to afford the desired product, cis-N-[3-(1-dimethylamino-4-hydroxy-2-oxo-2,4a,5,6,7,7a-hexahydro-1H-[1]pyrindin-3-yl)-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl]-methanesulfonamide hydrochloride (0.22 g, 0.43 mmol, 52%), as a white powder. 1H NMR (400 MHz, DMSO-d6) δ: 1.48-1.73 (2H, m), 1.88-2.20 (4H, m), 2.82 (6H, s), 3.06 (3H, s), 4.01 (1H, s), 7.49-7.74 (3H, m), 10.18 (1H, s). LC-MS (ESI) calcd for C18H23N5O6S2 469.54, found 470.2 [M+H+].

Quelle