These common heterocyclic compound, 53312-81-5, name is 5-Amino-2-fluorobenzonitrile, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Application In Synthesis of 5-Amino-2-fluorobenzonitrile
carboxylate as an off-white powder (382 mg). Methyl 3-chloro-1-methyl-4-[[1- (trifluoromethyl)cyclobutyl] sulfamoyl]pyrrole-2-carboxylate (150 mg, 0.4 mmol) and 5-amino- 2-fluorobenzonitrile (0.52 mmol) were dissolved in dry THF and cooled to 0C. Lithiumbis(trimethylsilyl)amide (1.24 mL, 1 M in THF, 1.24 mmol) was added dropwise and the reaction mixture was allowed to reach room temperature. After 1 hour lithium bis(trimethylsilyl)amide (0.5 mL, 1 M in THF, 0.5 mmol) was added and the reaction mixture was stirred for another hour. The volatiles were removed under reduced pressure and the residue was purified on silica gel using a heptane to EtOAc gradient. The collected fractions were evaporated todryness and the residue was crystallized from a heptane/EtOAc mixture yielding compound 221(91 mg) as off-white powder. Method D: Rt: 1.95mm mlz: 477.1 (M-H) Exact mass: 478.0. ?HNMR (400 MHz, DMSO-d6) oe ppm 1.75 – 1.88 (m, 2 H), 2.25 – 2.37 (m, 2 H), 2.41 – 2.48 (m, 2H), 3.79 (s, 3 H), 7.56 (t, J=9.1 Hz, 1 H), 7.68 (s, 1 H), 7.99 (ddd, J=9.2, 4.8, 2.6 Hz, 1 H), 8.20(dd, J=5.7, 2.6 Hz, 1 H), 8.61 (s, 1 H), 10.67 (s, 1 H).
The synthetic route of 5-Amino-2-fluorobenzonitrile has been constantly updated, and we look forward to future research findings.
Reference:
Patent; JANSSEN R&D IRELAND; VANDYCK, Koen; HACHE, Geerwin, Yvonne, Paul; LAST, Stefaan, Julien; MC GOWAN, David, Craig; ROMBOUTS, Geert; VERSCHUEREN, Wim, Gaston; RABOISSON, Pierre, Jean-Marie, Bernard; WO2014/184350; (2014); A1;,
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