One-pot synthesis of 2-aminobenzimidazoles using 2-chloro-1,3-dimethylimidazolinium chloride (DMC)

Discovery of 4-((2S,4S)-4-Ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic Acid (LNP023), a Factor B Inhibitor Specifically Designed To Be Applicable to Treating a Diverse Array of Complement Mediated Diseases

“…Initial efforts to develop SAR around the aminoimidazoline hit 1 relied heavily on the use of the reaction of chloro-1,3dimethylimidazolinium chloride (DMC-Cl) with the appropriate thiourea intermediate as outlined in Scheme 1. 55,56 For exploration around the imidazoline ring, substituted naphthylanilines of type A were converted to thiourea intermediates of type B, followed by DMC-Cl mediated condensation with the appropriate diamine or intramolecular cyclization with the pendant R 2 group to provide the final heterocyclic compounds (see Supporting Information and Scheme 1, for additional details). Indoleimidazolines 7−12 were generally prepared by similar sequences: tosyl-protected indoles C were converted to thioureas D, followed by condensation with ethylenediamine, deprotection, and optional C3-functionalization (see also Supporting Information and Scheme 1).…”

“…Initial efforts to develop SAR around the aminoimidazoline hit 1 relied heavily on the use of the reaction of chloro-1,3-dimethyl­imidazolinium chloride (DMC-Cl) with the appropriate thiourea intermediate as outlined in Scheme . , …”

Discovery of RAF265: A Potent mut-B-RAF Inhibitor for the Treatment of Metastatic Melanoma

“…4,5 For meta-substituted analogues, introduction of a fluorine at the 2-position gave a further boost in cellular potency (13,15). Unfortunately, all 3-and 5-alkyl substituted analogues suffered from poor exposure in pharmacokinetic (PK) studies.…”

“…Debus–Radziszewski cyclization with an in situ generated glyoxal derived from 1,1-dibromo-3,3,3-trifluoroacetone furnished the corresponding imidazole 9 . Reduction of the nitroarene followed by addition of 4-trifluoromethylphenyl thioisocyanate and FeCl 3 -promoted ring cyclization provided 1 . All compounds where biological data is presented have >95% purity as determined by HPLC.…”

“…12 Reduction of the nitroarene followed by addition of 4-trifluoromethylphenyl thioisocyanate and FeCl 3 -promoted ring cyclization provided 1. 13 All compounds where biological data is presented have >95% purity as determined by HPLC.…”