Sodium Hydroxide → 1-(5-{2-[(Ethylcarbamoyl)amino]-7-(pyridin-2-yl)-1,3-benzothiazol-5-yl}-1,2,4-thiadiazol-3-yl)-4-methylpiperidine-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

Ethyl 1-(5-{2-[(ethylcarbamoyl)amino]-7-(pyridin-2-yl)-1,3-benzothiazol-5-yl}-1,2,4-thiadiazol-3-yl)-4-methylpiperidine-4-carboxylate (100 mg, 0.13 mmol) was dissolved in EtOH (10 mL) and 2M aqueous NaOH (2.5 mL) was added and the mixture stirred at 90° C. for 18 h, cooled to rt and concentrated to ˜⅕ volume water (10 mL) and DCM (10 mL) added. The aqueous layer was separated and the organic layer discarded. The resultant aqueous layer was acidified to pH˜2 and extracted with DCM (3×10 mL), the combined organic layers were dried (MgSO4), filtered and concentrated in vacuo to give a brown solid which was purified by flash column chromatography (2× Biotage, SP4, 12 g, 2-8% MeOH, DCM) to afford Compound 233 as a cream solid (23 mg, 34%). 1H NMR (CDCl3) δ 8.70 (dd, J=4.8, 0.8 Hz, 1H), 8.62 (d, J=1.4 Hz, 1H), 8.44 (d, J=1.3 Hz, 1H), 8.09 (d, J=8.2 Hz, 1H), 7.78 (td, J=7.8, 1.8 Hz, 1H), 7.22 (ddd, J=7.4, 4.9, 0.8 Hz, 1H), 3.83 (brs, 2H), 3.39-3.29 (m, 5H), 2.22 (d, J=13.3 Hz, 2H), 1.70-1.40 (m, 4H), 1.19 (t, J=7.3 Hz, 4H), 0.86 (t, J=7.5 Hz, 3H). MS: 524.06 [M+H]+.

Provenance & Evidence