3-Methyl-5-isoxazolecarboxylic acid → HCID 24955179, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 5-methylisoxazole-3-carboxylic acid (8.6 mg, 68 μmol), diisopropylethylamine (12 μL, 68 μmol), and 2-chloro-5-(1-((R)-1-(3-chlorophenyl)ethylamino)ethyl)benzenamine 109 (21 mg, 68 μmol) in DMF was stirred under N2 and chilled to 0° C. HATU (26 mg, 68 μmol) was then added to the solution. The reaction was allowed to warm to room temperature and stirred for 3 h. Afterwards, the reaction was diluted with water and EtOAc. The organic solution was extracted with saturated NaHCO3, water, and brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified by silica gel chromatography using a 5% to 60% gradient of EtOAc in hexanes as the eluent. The desired fractions were combined and concentrated to give N-(2-chloro-5-(1-((R)-1-(3-chlorophenyl)ethylamino)ethyl)phenyl)-5-methylisoxazole-3-carboxamide 110 (20 mg, 70% yield) as a colorless oil and as a mixture of diastereomers. 1H NMR (400 MHz, MeOH) δ ppm 1.60-1.66 (m, 6H) 2.53 (s, 3H) 4.19 (m, 2H) 6.61 (s, 1H) 7.19 (dd, J=8.31, 2.05 Hz, 1H) 7.30 (m, 1H) 7.40 (s, 1H) 7.48 (d, J=4.89 Hz, 2H) 7.63 (d, J=8.41 Hz, 1H) 8.09 (s, 1H). Mass spectrum: calculated for C21H21Cl2N3O2 418.3. found 418.4 (M++1).

Provenance & Evidence