Three leflunomide metabolite analogs

The title compounds, 1-cyano-2-hydroxy-N-[4-(methylsulfon­yl)phenyl]but-2-en­amide, C12H12N2O4S, PHI492, 1-cyano-2-hydroxy-N-[3-(methyl­sulfonyl)­phenyl]­but-2-en­amide, C12H12­N2O4S, PHI493, and N-[3-bromo-4-(trifluoro­methoxy)­phenyl]-1-cyano-2-hydroxybut-2-en­amide, C12H8Br­F3N2O3, PHI495, are potent inhibitors of Bruton's tyrosine kinase (BTK). The molecular structures of these compounds are similar and they display similar hydrogen-bonding networks and crystal packing. Examination of the crystal-packing interaction in the three compounds reveals an alternating direction of adjacent mol­ecules in the crystalline lattice due to intermolecular cyano–amide hydrogen bonding. PHI492, a positional isomer of PHI493, does not form intermolecular O—H⋯O hydrogen bonds between mol­ecules and crystallizes in a space group different from that of PHI493 and PHI495. The aromatic ring and the amide group of each mol­ecule form a conjugated π-system which ensures planarity, with further stabilization gained from intramolecular O—H⋯O hydrogen bonds.