5-Bromo-2,4,6-trichloropyrimidine

5-Bromo-2, 4, 6-trichloropyrimidine (1.880 g, 6.81 mmol) was dissolved in THF (11 mL) and water (5 mL), and sodium acetate (1.68 g, 20.4 mmol), followed by 4-fluoroaniline (787 mg, 0.68 mL, 6.87 mmol) were added. The mixture was stirred at room temperature for 18 h. After that, a saturated aqueous solution of sodium hydrogencarbonate (15 mL) was added and the resulting mixture was extracted with ethyl acetate (2 x 150 mL). The combined organic layers were dried (sodium sulfate) and concentrated in vacuo. The crude was purified by column chromatography (silica gel, 40 g, eluting with ethyl acetate / n-heptane, gradient 0: 100 to 10:90) to afford, after drying in vacuo (40C, 5 mbar), the title compound as a light brown solid (2.07 g, 90%). HPLC (method LCMS_fastgradient) tR = 1.36 min. 1H NMR (CDC13, 300 MHz): delta 7.12 (dd, / = 8.3, 9.1 Hz, 2 H), 7.43 (br s, 1 H), 7.52 (dd, / = 4.6, 8.9 Hz, 2 H). MS (ES+) m/z 335.9, 337.9, 339.9 [M+H, Br & 2 CI isotopes] .5-Bromo-2, 4, 6-trichloropyrimidine (1.880 g, 6.81 mmol) was dissolved in THF (11 mF) and water (5 mF), and sodium acetate (1.68 g, 20.4 mmol), followed by 4-fluoroaniline (787 mg, (0231) 0.68 mF, 6.87 mmol) were added. The mixture was stirred at room temperature for 18 h. After that, a saturated aqueous solution of sodium hydrogenocarbonate (15 mF) was added and the resulting mixture was extracted with ethyl acetate (2 x 150 mF). The combined organic layers were dried (sodium sulfate) and concentrated in vacuo. The crude was purified by column chromatography (silica gel, 40 g, eluting with ethyl acetate / n-heptane, gradient 0:100 to 10:90) to afford, after drying in vacuo (40C, 5 mbar), the title compound as a light brown solid (2.07 g, 90%). MS (ES+) m/z 335.9, 337.9, 339.9 [M+H, Br & 2 Cl isotopes].2-Chloro-4-fluoroaniline (512 mg, 0.42 mL, 3.45 mmol) was dissolved in THF (10 mL), the solution was cooled to 0-5C (ice bath) and a solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran / ethylbenzene (1.0 M, 3.4 mL, 3.4 mmol) was added. After stirring for 15 min at 0-5C, a solution of 5-Bromo-2, 4, 6-trichloropyrimidine (2.30 g, 8.33 mmol) was dissolved in THF (14 mL) and water (7 mL), and sodium acetate (2.05 g, 25.0 mmol), followed by 2, 3-difluoroaniline (1.15 g, 0.90 mL, 8.7 mmol) were added. The mixture was stirred at room temperature for 18 h. After that, a saturated aqueous solution of sodium hydrogencarbonate (20 mL) was added and the resulting mixture was extracted with ethyl acetate (2 x 100 mL). The combined organic layers were dried (sodium sulfate) and concentrated in vacuo. The crude was purified by column chromatography (silica gel, 80 g, eluting with ethyl acetate / n-heptane, gradient 0: 100 to 10:90) to yield, after drying in vacuo (40C, 5 mbar), the title compound as a light brown solid (1.23 g, 42%). HPLC (method LCMS_fastgradient) tR = 1.38 min. 1H NMR (CDC13, 300 MHz): delta 6.97- 7.09 (m, 1 H), 7.13-7.23 (m, 1 H), 7.72 (br s, 1 H), 8.03-8.11 (m, 1 H). MS (ES+) m/z 353.8, 355.8, 357.8 [M+H, Br & 2 CI isotopes].4-Fluoro-N-(3-methylbut-3-en-l-yl)aniline (Int-24, 382 mg, 2.13 mmol) was dissolved in (0285) THF (4 mL) and water (2 mL), and sodium acetate (525 mg, 6.39 mmol), followed by 5-bromo- 2, 4, 6-trichloropyrimidine (589 mg, 2.13 mmol) were added. The mixture was stirred at room temperature for 18 h. After that, a saturated aqueous solution of sodium hydrogencarbonate (10 mL) was added and the resulting mixture was extracted with ethyl acetate (2 x 80 mL). The combined organic layers were dried (sodium sulfate) and concentrated in vacuo. The crude was purified by column chromatography (silica gel, 40 g, eluting with ethyl acetate / n-heptane, gradient 0: 100 to 5:95) to yield, after drying in vacuo (40C, 5 mbar), the title compound as a yellow solid (527 mg, 61 ). HPLC (method LCMS_fastgradient) tR = 1.70 min. 1H NMR (CDC13, 300 MHz): delta 1.79 (s, 3 H), 2.32-2.40 (m, 2 H), 4.01-4.08 (m, 2 H), 4.67-4.71 (m, 1 H), 4.78-4.82 (m, 1 H), 7.06-7.11 (m, 4 H). MS (ES+) m/z 404.1, 406.1, 408.1 [M+H, Br & 2 CI isotopes].5-Bromo-2, 4, 6-trichloropyrimidine (1.30 g, 4.96 mmol) and 3-(trifluoromethyl)- bicyclo[l.l. l]pentan-l- amine hydrochloride (985 mg, 4.99 mmol) were suspended in acetonitrile (6.5 mL) and N, N-diisopropylethylamine (1.55 g, 2.1 mL, 12 mmol) was added at room temperature. The resulting yellow solution was stirred for 7 h at room temperature. After that, the reaction mixture was concentrated in vacuo and the residue was purified by column chromatography (silica gel, 80 g, eluting with ethyl acetate / n-heptane, gradient 0: 100 to 10:90) to yield, after drying in vacuo (40C, 5 mbar), the title compound as an off-white solid (1.487 g, 80%). HPLC (method LCMS_fastgradient) tR = 1.50 min. 1H NMR (CDC13, 300 MHz): delta 2.46 (s, 6 H), 6.10 (br s, 1 H). MS (ES+) m/z 375.9, 377.9, 379.8 [M+H, Br & 2 CI isotopes].5-Bromo-2, 4, 6-trichloropyrimidine (1.28 g, 4.88 mmol) and 3, 3-difluorocyclobutan- amine hydrochloride (715 mg, 4.98 mmol) were suspended in acetonitrile (6 mL) and N, N- diisopropylethylamine (1.55 g, 2.1 mL, 12 mmol) was added at room temperature. The resulting yellow solution was stirred for 7 h at room temperature. After that, the reaction mixture was concentrated in vacuo and the residue was purified by column chromatography (silica gel, 80 g, eluting with ethyl acetate / n-heptane, gradient 0: 100 to 10:90) to yield, after drying in vacuo (40C, 5 mbar), the title compound as a pale yellow oil (1.188 g, 73%). HPLC (method (0254) LCMS_fastgradient) tR = 1.31 min. 1H NMR (CDC13, 300 MHz): delta 2.48-2.67 (m, 2 H), 3.08-3.25 (m, 2 H), 4.39-4.53 (m, 1 H), 5.78-5.90 (m, 1 H). MS (ES+) m/z 330.0, 332.0, 334.0 [M+H, Br & 2 CI isotopes] .5-Bromo-2, 4, 6-trichloropyrimidine (2.50 g, 9.05 mmol) was dissolved in THF (16 mL) and water (8 mL), and sodium acetate (2.23 g, 27.2 mmol), followed by 2, 4-difluoroaniline (1.18 g, 0.92 mL, 9.14 mmol) were added. The mixture was stirred at room temperature for 18 h. After that, a saturated aqueous solution of sodium hydrogencarbonate (30 mL) was added and the resulting mixture was extracted with ethyl acetate (2 x 150 mL). The combined organic layers were dried (sodium sulfate) and concentrated in vacuo. The crude was purified by column chromatography (silica gel, 120 g, eluting with ethyl acetate / n-heptane, gradient 0: 100 to 5:95) to yield, after drying in vacuo (40C, 5 mbar), the title compound as an off-white solid (2.22 g, 69%). HPLC (method LCMS_fastgradient) tR = 1.39 min. 1H NMR (CDC13, 300 MHz): delta 6.91- 7.03 (m, 2 H), 7.56 (br s, 1 H), 8.16 (ddd, 7 = 5.8, 9.7, 9.7 Hz, 1 H). MS (ES+) m/z 353.9, 355.9, 357.9 [M+H, Br & 2 CI isotopes].5-Bromo-2, 4, 6-trichloropyrimidine (3.00 g, 10.9 mmol) was dissolved in THF (18 mL) and water (9 mL), and sodium acetate (2.67 g, 32.6 mmol), followed by 3, 4-difluoroaniline (1.43 g, 1.10 mL, 11.1 mmol) were added. The mixture was stirred at room temperature for 18 h. After that, a saturated aqueous solution of sodium hydrogencarbonate (30 mL) was added and the resulting mixture was extracted with ethyl acetate (2 x 150 mL). The combined organic layers were dried (sodium sulfate) and concentrated in vacuo. The crude was purified by column chromatography (silica gel, 120 g, eluting with ethyl acetate / n-heptane, gradient 0: 100 to 10:90) to afford, after drying in vacuo (40C, 5 mbar), the title compound as a light yellow solid (3.32 g, 86%). HPLC (method LCMS_fastgradient) tR = 1.37 min. 1H NMR (CDC13, 300 MHz): delta 7.17- 7.24 (m, 2 H), 7.43 (br s, 1 H), 7.59-7.68 (m, 1 H). MS (ES+) m/z 353.9, 355.9, 357.8 [M+H, Br & 2 CI isotopes] .

Molecular Weight:262.31
XLogP3:3.8
Hydrogen Bond Acceptor Count:2
Exact Mass:259.83104
Monoisotopic Mass:259.83104
Topological Polar Surface Area:25.8
Heavy Atom Count:10
Complexity:113
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes