Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole, A new synthetic method of this compound is introduced below., SDS of cas: 1003-21-0
Isopropylmagnesium chloride lithium chloride complex (1.3 M in tetrahydrofuran, 2.0 mL, 2.60 mmol) was added to an ice-water cooled solution of 5-bromo-1-methyl-1H-imidazole (444 mg, 2.76 mmol) in tetrahydrofuran (12 mL). The resulting white suspension was stirred for 5 minutes then the cooling bath was removed. After 10 minutes, the suspension was added dropwise by syringe to an ice-water cooled mixture of (3-(4-(1H-1,2,4-triazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(4-chlorophenyl)methanone (772 mg, 1.59 mmol, Intermediate 45, step e) and lanthanum(III) chloride bis(lithium chloride) complex solution (0.6 M in tetrahydrofuran, 5.25 mL, 3.16 mmol) in tetrahydrofuran (15 mL). After 20 minutes, saturated aqueous ammonium chloride solution was added (2 mL) then the cooling bath was removed. The mixture was diluted with water (25 mL) and ethyl acetate (50 mL). The layers were separated. The aqueous layer was extracted with ethyl acetate (25 mL). The organic layers were combined and the combined solution was dried with sodium sulfate. The dried solution was filtered and the filtrate was absorbed onto 6 g of silica gel for dry-load flash-column chromatography on silica gel eluting with 100% dichloromethane initially for 5 minutes, grading to 7% methanol-dichloromethane over 30 minutes to afford the titled compound as a white solid. 1H NMR (400 MHz, CDCl3) delta ppm 8.43 (s, 1H), 8.12 (d, J=2.1 Hz, 1H), 8.06 (s, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.58-7.50 (m, 3H), 7.41 (d, J=8.5 Hz, 2H), 7.36 (d, J=1.1 Hz, 1H), 7.31 (s, 4H), 6.38 (d, J=1.1 Hz, 1H), 4.33 (s, 2H), 4.12 (s, 1H), 4.08 (s, 3H), 3.38 (s, 3H); MS m/e 571.1 [M+H]+. (3-(4-(iH-i,2,4-triazol-i-yl)ben- zyl)-4-chloro-2-methoxyquinolin-6-yl)(4-chlorophenyl)(i – methyl-iH-imidazol-5-yl)methanol was purified by HPEC (Chiralpak IA column, 50 mmx2SO mm, ethanol with 0.2% triethylamine as eluent, 30 mE/minute, 254 nm wavelength) to give two enantiomers. The first eluting enantiomer was Example 648: ?H NMR (400 MHz, CDC13) oe ppm 8.43 (s, iH), 8.12 (d, J=2.i Hz, iH), 8.06 (s, iH), 7.78 (d, J=8.7 Hz, iH), 7.56-7.50 (m, 3H), 7.41 (d, J=8.5 Hz, 2H), 7.36 (d, J=i .1 Hz, iH), 7.31 (s, 4H), 6.38 (d, J=i.i Hz, iH), 4.33 (s, 2H), 4.08 (s, 3H), 3.38 (s, 3H); MS mle 571.1 [M+H]+ and the second eluting enantiomer was Example 64C: ?H NMR (400 MHz, CDC13) oeppm8.43 (s, iH), 8.12 (d, J=2.i Hz, iH), 8.06 (s, iH), 7.78 (d, J=8.7 Hz, iH), 7.58-7.49 (m, 3H), 7.41 (d, J=8.6 Hz, 2H), 7.35 (s, iH), 7.31 (s, 4H), 6.38 (s, iH), 4.33 (s, 2H), 4.21 (s, iH), 4.08 (s, 3H), 3.38 (s, 3H); MS mle 571.1 [M+H] +.
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Patent; Janssen Pharmaceutica NV; Leonard, Kristi A.; Barbay, Kent; Edwards, James P.; Kreutter, Kevin D.; Kummer, David A.; Maharoof, Umar; Nishimura, Rachel; Urbanski, Maud; Venkatesan, Hariharan; Wang, Aihua; Wolin, Ronald L.; Woods, Craig R.; Pierce, Joan; Goldberg, Steven; Fourie, Anne; Xue, Xiaohua; US2014/107094; (2014); A1;,
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