Triethylamine → (S)-N-(1-(4-chlorophenyl)-5-isopropyl-1H-pyrazol-4-yl)-2-(2-methyl-4-(trifluoromethyl)-1H-imidazol-1-yl)propanamide

Participants

Reaction Steps

To a solution of the acid intermediate from step d (23.6 mg, 0.1 mmol) and 1-(4-chlorophenyl)-5-isopropyl-1H-pyrazol-4-amine (16.6 mg, 0.064 mmol) in DMF (0.5 mL) was added Et3N (20 μL, 0.13 mmol) and HATU (31.6 mg, 0.083 mmol). After stirring 35 min, the slurry was concentrated under reduced pressure and the residue was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent). The residue was neutralized and salted with HCL to provide the titled compound hydrochloride salt as a colorless solid (12.3 mg). 1H NMR (400 MHz, CD3OD) δ 8.28 (d, J=1.6 Hz, 1H), 7.63 (s, 1H), 7.57 (ddd, J=9.7, 5.1, 3.1 Hz, 2H), 7.41 (ddd, J=9.7, 5.0, 3.1 Hz, 2H), 5.38 (q, J=7.0 Hz, 1H), 3.03 (hept, J=7.0 Hz, 1H), 2.65 (s, 3H), 1.91 (d, J=7.0 Hz, 3H), 1.23 (d, J=7.1 Hz, 3H), 1.22 (d, J=7.0 Hz, 3H); MS: (ES) m/z calculated for C20H22ClF3N5O [M+H]+ 440.1, found 439.9. Retention time on chiral HPLC: 5.9 min (RegisPack cat#783104, 25 cm×4.6 mm, 5 micron; eluent: 0.1% diethylamine/IPA, 1.0 ml/min). The er is determined to be 20:1 with the (R)-enantiomer having a retentime of 3.4 min. Absolute configuration of the (R)-enantiomer was confirmed by an independent synthesis from methyl (L)-lactate.

Provenance & Evidence