Sodium ethoxide → N-[3-[(4aR,7aS)-1-[(3-chloro-4-fluoro-phenyl)methyl]-4-hydroxy-2-oxo-5,6,7,7a-tetrahydro-4aH-cyclopenta[b]pyridin-3-yl]-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]methanesulfonamide

Participants

Reaction Conditions

Reaction Steps

(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 (crude from Example 11b, 0.252 g, 0.42 mmol) was dissolved in ethanol (8.4 mL), followed by addition of a 21% w/w solution of sodium ethoxide in ethanol (0.545 mL, 1.68 mmol), and heated to 60° C. for 1 h. Upon cooling, the reaction mixture was then quenched with 1.0 M aqueous hydrochloric acid solution (2 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were dried over magnesium sulfate, filtered, and dried in vacuo. Recrystallization from 10-20% ethyl acetate in hexanes afforded the desired product, (4aR,7aS)-N-{3-[1-(3-chloro-4-fluoro-benzyl)-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 (0.147 g, 0.259 mmol, 61%), as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 1.51-1.58 (m, 3H), 1.99-2.00 (m, 3H), 3.06 (s, 3H), 3.30 (bs, 1H), 3.88 (bs, 1H), 4.47 (d, 1H, J=15.0 Hz), 4.89 (d, 1H, J=15.4 Hz), 7.36 (d, 2H, J=7.3 Hz), 7.50 (dd, 1H, J1=8.6 Hz, J2=2.4 Hz), 7.57-7.59 (m, 3H), 10.17 (bs, 1H). LC-MS (ESI) calcd for C23H22ClFN4O6S2 568.07, found 569.03 [M+H+].

Provenance & Evidence