1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-(adamantan-1-ylmethoxy)-5-chloro-2-fluoro-N-(morpholinosulfonyl)-benzamide

To a mixture of 4-(adamantan-1-ylmethoxy)-5-chloro-2-fluorobenzoic acid (0.17 g, 0.50 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.22 g, 1.15 mmol) and 4-dimethylaminopyridine (0.14 g, 1.15 mmol) in anhydrous dichloromethane (10 mL) was added morpholine-4-sulfonamide (0.17 g, 1.0 mmol) at ambient temperature. The resulting mixture was stirred at ambient temperature for 16 h. The mixture was quenched with hydrochloride acid (1N, 30 mL) followed by extraction with ethyl acetate (100 mL). The organic layer was washed with water (30 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuo, the residue was purified by silica gel column chromatography using 10-60% gradient ethyl acetate (containing 0.2% acetic acid) in hexanes to afford the title compound as an off-white solid (0.05 g, 20%): 1H NMR (300 MHz, DMSO-d6) δ 7.88 (s, 1H), 6.88 (s, 1H), 4.06 (d, J=6.8 Hz, 2H), 3.39 (s, 3H), 2.50-2.42 (m, 1H), 2.12-2.05 (m, 1H), 1.98-1.94 (m, 1H), 1.90-1.68 (m, 4H), 1.50-1.41 (m, 2H), 1.22 (s, 3H), 0.87 (s, 3H); MS (ES−) m/z 397.2, 399.2 (M−1); MS (ES+) m/z 399.1, 401.1 (M+1);

1. customThe mixture was quenched with hydrochloride acid (1N, 30 mL)
2. extractionfollowed by extraction with ethyl acetate (100 mL)
3. washThe organic layer was washed with water (30 mL)
4. dry with materialdried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationThe filtrate was concentrated in vacuo
7. customthe residue was purified by silica gel column chromatography

ORD-Eintrag

ord-f1be3a03abd9480e84260a2877576a47

Quelldatensatz

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08952169B2