Diisopropylethylamine → HCID 178522225, Verbindung

Step (c) A flask was charged with (S)-benzyl 3-(4-(4-fluorophenoxy)phenylcarbamoyl)piperazine-1-carboxylate (1.08 g, 2.41 mmol), 4-imidazoleacetic acid hydrochloride (392 mg, 2.41 mmol), DIEA (1.0 mL, 5.8 mmol), HATU (1.01 g, 2.65 mmol) and DMF (5 mL). The reaction mixture was stirred at ambient temperature for 20 minutes and then quenched with saturated sodium bicarbonate (aq., 10 mL). The mixture was extracted with ethyl acetate (20 mL) and the extract was washed with deionized water (10 mL) and then brine (10 mL), dried over anhydrous sodium sulfate, filtered and concentrated. Product was purified from the residue by reverse phase HPLC to give Compound 257, (S)-benzyl 4-(2-(1H-imidazol-4-yl)acetyl)-3-(4-(4-fluorophenoxy)phenylcarbamoyl)piperazine-1-carboxylate (0.80 g, 1.43 mmol, 67% yield), as an off-white solid. 1H-NMR (400 MHz, CDCl3): 10.27 (s, 1H), 9.18 (s, 1H), 7.60-7.49 (m, 3H), 7.47-7.21 (m, 5H), 7.06-6.91 (m, 6H), 5.45 (s, 1H), 5.17 (s, 2H), 5.09-5.00 (m, 2H), 4.04 (m, 2H), 4.09-3.97 (m, 2H), 3.81-3.73 (m, 2H), 3.46-3.77 (m, 1H), 3.17 (dd J=13.6, 4.8 Hz, 1H), 3.13-3.00 (m, 1H). MS (EI) for C30H28FN5O5. found 558.2 (MH+).

1. customquenched with saturated sodium bicarbonate (aq., 10 mL)
2. extractionThe mixture was extracted with ethyl acetate (20 mL)
3. washthe extract was washed with deionized water (10 mL)
4. dry with materialbrine (10 mL), dried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customProduct was purified from the residue by reverse phase HPLC

ORD-Eintrag

ord-83a2de370aa949b5b76efe94b21e7da0

Quelldatensatz

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08791102B2