Related Products of 1003-21-0, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 1003-21-0 as follows.
Example 14a: 4-((3-(4-(1H-1,2,4-triazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(hydroxy)(1-methyl-1H-imidazol-5-yl)methyl)benzonitrile A solution of isopropylmagnesium chloride-lithium chloride complex in tetrahydrofuran (1.3 M, 0.986 mL, 1 ,28 mmol) was added dropwise to an ice-water cooled, stirring suspension of 5- bronio-1 -methyl- IH- imidazole (241 mg, 1.50 mmol) in dry tetrahydrofuran (6 mL). After 5 minutes, the flask was removed from the cooling bath and the white suspension was stirred at 23 C. After 10 minutes, the Grignard suspension was added to an ice-water cooled, stirring mixture containing 4-(3-(4-( IH- 1 ,2,4-triazol- 1 -yl)benzyl)-4-chloro-2-methoxyquinoline-6- carbonyl)benzonitrile (205 mg, 0.427 mmol, Intermediate 16: step e) and lanthanum(III) chloride bis(lithium chloride) complex (0.6 M solution in tetrahydrofuran, 1.42 mL, 0.854 mmol) in dry tetrahydrofuran (8 mL), After 20 minutes, 1 M aqueous citric acid solution (1 niL) was added. The flask was removed from, the cooling bath and then ethyl acetate (100 mL) was added. Additional 1 M aqueous citric acid solution (-15 mL) was added until the mixture was comprised of two homogeneous layers, at which point saturated aqueous sodium bicarbonate solution was added until the H of the aqueous layer was ~8 by litmus paper test. The layers were separated. The aqueous layer was extracted with ethyl acetate (20 mL). The organic layers were combined and the combined solution was dried over sodium sulfate. The dried solution was filtered. Silica gel (5 g) was added to the filtrate and the mixture was concentrated by rotary evaporation to afford a free-flowing powder. The powder was loaded onto a silica gel column for flash-column chromatography purification. Elution with dichloromethane initially, grading to 50% methanol–dich.lorometh.ane provided the title compound as a w hite solid. H NMR (5001 MHz, CDCI3) delta ppm 8.45 (s, 1H), 8.10 (d . ./ 2.2 Hz, 1 I S). 8.0(S (s, U S). 7.81 (d, ,/ 8.8 Hz, 1H), 7.65 (d, J = 8.5 Hz, 2H), 7.58-7.51 (m, 5H), 7.44-7.38 (m, 3H), 6.41 (d, ,7 = 1.1 Hz, 1H), 4.33 (s, 2H), 4.09 (s, 3H), 3.94 (s, 1H), 3.38 (s, 3H); MS (ESI): mass calcd. C31H24CIN7O2, 561.2; m/z found, 562.1 [M+H]+.4-((3-(4-(l H-l ,2,4-Triazol-l-yl)benzyl)-4-chloro-2-methoxyquinolin-6lH-imidazol-5-yl)methyl)benzonitrile was purified by chiral SFC (Chiralpak AD-H column, 5 mupiiota, 250 mm. 20 mm, mobile phase: 60% C02, 40% methanol) to give two enantiomers. The first eluting enantiomer was Example 14b:3H NMR (500 MHz, CDCI3) delta ppm 8.44 (d, J = 1.0 Hz, 1H), 8.10 (d, J= 2.1 Hz, 1 H), 8.06 (s, 1 H), 7.81 (d, J= 8.7 Hz, 1H), 7.66 (d, J= 8.2 Hz, 2H), 7.58-7.50 (m, 5H), 7.44-7.38 (m, 3H), 6.42 (s, 1H), 4.33 (s, 2H), 4,09 (s, 3H), 4.02-3.81 (br s, 1 H), 3.38 (s, 3H); MS (ESI): mass calcd. C31H24CIN7O2, 561.2; m/z found, 562.3 [M+H]+ and the second eluting enantiomer was Example 14c: H NMR (500 MHz, CDCI3) delta ppm. 8.45 (s, I I I). 8.09 (d, J —— 2.2 Hz, 1 H), 8.06 (s, IH), 7.85 (d, ./ 8.9 Hz, 1H), 7.66 (d, ./ = 8.1 Hz, 21 1).7.58-7.51 (m, 5H), 7.45-7.38 (m, 3H), 6.43 (s, 5 H), 4.33 (s, 2H), 4.09 (s, 3H), 3.38 (s, 3H); MS (ESI): mass calcd. C31H24CIN7O2, 561 .2; m/z found, 562.3 [M+H]+.
According to the analysis of related databases, 1003-21-0, the application of this compound in the production field has become more and more popular.
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.; FOURIE, Anne; XUE, Xiaohua; CUMMINGS, Maxwell D.; JONES, William Moore; GOLDBERG, Steven; WO2015/57205; (2015); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem