On August 18, 2005, Buchstaller, Hans-Peter; Burgdorf, Lars; Stieber, Frank; Amendt, Christiane; Grell, Matthias; Sirrenberg, Christian; Zenke, Frank published a patent.COA of Formula: C9H5F3N2O2 The title of the patent was Preparation of 1,3-diarylureas as inhibitors of raf and other kinases useful against cancer and other diseases. And the patent contained the following:
The present invention relates to bisarylurea derivatives (shown as I; variables defined below; e.g. 4-[4-[3-[4-chloro-5-methyl-2-(2-methylaminoethoxy)phenyl]ureido]phenoxy]pyridine-2-carboxylic acid methylamide (shown as II)), their use as inhibitors of raf-kinase (no data) and for the manufacture of a pharmaceutical composition and a method of treatment, comprising administering said pharmaceutical composition to a patient. Methods of preparation are claimed and >100 example preparations are included. For example, 1-[2-[2-[(tert-butoxycarbonyl)(methyl)amino]ethoxy]-5-(trifluoromethyl)phenyl]-3-[4-[[2-(methylcarbamoyl)pyridin-4-yl]oxy]phenyl]urea was prepared (87 %) by reacting tert-Bu [2-[2-amino-4-(trifluoromethyl)phenoxy]ethyl](methyl)carbamate (preparation given) with p-nitrophenyl chloroformate followed by N-methyl-4-(4-aminophenoxy)pyridine-2-carboxamide (preparation given) and DIPEA; deprotection gave 86 % 1-[2-[2-(methylamino)ethoxy]-5-(trifluoromethyl)phenyl]-3-[4-[[2-(methylcarbamoyl)pyridin-4-yl]oxy]phenyl]urea. For I: Ar1, Ar2 = aromatic hydrocarbons containing 6 to 14 C atoms and ethylenic unsaturated or aromatic heterocyclic residues containing 3 to 10 C atoms and one or two heteroatoms, = N, O and S; E, G, M, Q and U = C and N atoms, with the proviso that ≥1 of E, G, M, Q and U are C atoms and that X is bonded to a C atom. R7 = Het, OHet, N(R11)Het, (CR5R6)kHet, et al. or R7 = -SO2-CR8:CR8-, wherein both valencies are bound vicinally to Ar1; R8, R9 and R10 = H, A, cycloalkyl comprising 3 to 7 C atoms, Hal, et al.; Y = O, S, NR21, C(R22)-NO2, C(R22)-CN and C(CN)2; g = 1-3, preferably 1 or 2, p, r = 0-5; q = 0-4, preferably 0, 1 or 2; addnl. details are given in the claims. The experimental process involved the reaction of 2-(2-Nitro-4-(trifluoromethyl)phenyl)acetonitrile(cas: 13544-06-4).COA of Formula: C9H5F3N2O2
The Article related to aryl urea preparation raf kinase inhibitor antitumor agent, Heterocyclic Compounds (One Hetero Atom): Pyridines and other aspects.COA of Formula: C9H5F3N2O2
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts