Reference of 53312-81-5, 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.
Lithium bis(trimethylsilyl)amide in toluene (0.59 mL, 1 M, 0.59 mmol) was added to ethyl 3 -fluoro- 1 -methyl-4-[ [1 -(trifluoromethyl)cyclopentyl]sulfamoyl] pyrrole-2-carboxylate (57 mg, 0.148 mmol) and 5-amino-2-fluoro-benzonitrile (26.1 mg, 0.19 mmol) in THF (10 mL) at room temperature under nitrogen. The reaction mixture was stirred 1 hour, quenched with NH4C1(25 mL) solution, diluted with brine (25 mL) and extracted with EtOAc (50 mL). The organic layer was dried over magnesium sulphate, filtered and concentrated. The residue was purified by silica gel column chromatography using a gradient from 10 to 100% EtOAc in heptane. The product fractions were concentrated. The residue was dissolved in hot methanol (10 mL). The product crystallised upon addition of water. Compound 281 (30.5 mg) was filtered off and driedovernight in vacuo at 50C. Method D: Rt: 2.02 mm mlz: 475.3 (M-H) Exact mass: 476.1. ?HNMR (400 MHz, DMSO-d6) oe ppm 1.42 – 1.54 (m, 2 H), 1.58 – 1.71 (m, 2 H), 1.72 – 1.85 (m, 2H), 2.21 – 2.32 (m, 2 H), 3.81 (s, 3 H), 7.50 – 7.57 (m, 2 H), 7.97 (ddd, J=9.2, 4.8, 2.9 Hz, 1 H),8.17 (dd, J=5.8, 2.8 Hz, 1 H), 8.32 (s, 1 H), 10.33 (s, 1 H). Differential scanning calorimetry:From 30 to 300 C at 10C/mm: peak at 187.0 C.
The synthetic route of 53312-81-5 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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