Introduction of a new synthetic route about 1196152-38-1

Statistics shows that 2-Bromo-5-(trifluoromethyl)pyrazine is playing an increasingly important role. we look forward to future research findings about 1196152-38-1.

Electric Literature of 1196152-38-1, These common heterocyclic compound, 1196152-38-1, name is 2-Bromo-5-(trifluoromethyl)pyrazine, 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.

Example 44k (300 mg, 0.8 mmol), 2-Chloro-5-(trifluoromethyl)pyrimidine (199 mg, 1.09 mmol) and N,N-diisopropylethylamine (287 mul, 1.67 mmol) are dissolved in 4 ml of anhydrous DMSO and heated in a microwave reactor during 30 minutes at 150C. The crude is partitioned between EtOAc and water, the organic layer is dried over anhydrous Na2S04 then concentrated under reduced pressure to obtain 360 mg of the title product. HPLC-MS (Method 10): Rt = 3. MS (ES+): m/z = 505 [M+H]+ . The enantiomers are obtained by HPLC using a chiral stationary phase. Method for separation: HPLC apparatus type: Waters 600 Pump; column: Daicel Chiralpack AD-H, 5.0 muiotaeta, 250 mm x 20 mm; method: eluent hexane/ IPA 70:30; flow rate: 15 mL/min, Temperature: 25 C; UV Detection: 254 nm Example of separation by chiral HPLC: Submitted to separation: 665 mg of Example 1 prepared as described above; Obtained: 157 mg of enantiomer 1 (Exp. 2) and 40 mg of enantiomer 2 (Exp. 3). Example 34 is synthesized as described for example 1 starting from example 44f (80 mg, 0.22 mmol) instead of example 44k, 2-Bromo-5-(trifluoromethyl)pyrazine (75 mg, 0.33 mmol) instead of 2-Chloro-5-(trifluoromethyl)pyrimidine, N,N-diisopropylethylamine (75 mu, 0.44 mmol) and 1 ml of anhydrous DMSO. The reaction mixture is heated in a microwave reactor at 130C during 30 minutes. After the work-up, the crude product is purified by Silica gel flash chromatography using cyclohexane/EtOAc 20:80 to 0: 100 as eluent to obtain the title compound (83 mg, 74 % yield). HPLC-MS (Method 5): Rt = 2.96 min MS (APCI+): m/z = 505 [M+H]+ .

Statistics shows that 2-Bromo-5-(trifluoromethyl)pyrazine is playing an increasingly important role. we look forward to future research findings about 1196152-38-1.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; HOENKE, Christoph; GIOVANNINI, Riccardo; LESSEL, Uta; ROSENBROCK, Holger; SCHMID, Bernhard; WO2015/55698; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem