Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 23399-70-4, name is 5-Chloro-2-iodotoluene, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C7H6ClI
Intermediate 6: 2:1 Mixture of 2-(bromomethyl)-4-chloro-1-iodobenzene and 1- bromo-2-(bromomethyl)-4-chlorobenzene; Lambda/-bromosuccinimide (6.34 g, 35.6 mmol) was weighed into a flask and carbon tetrachloride (200 ml) was added followed by 4-chloro-1-iodo-2-methylbenzene (8.57 g, 33.9 mmol, Fluorochem Ltd). The reaction mixture was stirred and dibenzoyl peroxide (0.822 g, 3.39 mmol) was added in one portion. The apparatus was then flushed three times with nitrogen and heated to reflux with vigorous stirring. After approximately 46 h at reflux, the reaction was allowed to cool to room temperature. The reaction mixture was filtered to remove the insoluble material and washed with aqueous sodium sulfite solution. The carbon tetrachloride layer was dried over sodium sulfate and evaporated to give a crude product as a pale yellow oil which crystallised on standing. The crude product was triturated with cyclohexane. The white insoluble material (1.30 g) was retained. The soluble material was then loaded onto 50 g silica SPE (pre-conditioned with cyclohexane) and was eluted with cyclohexane. Two product batches were obtained from this purification. The slower running material was obtained as a clear liquid which crystallised on standing to give the title compounds as a 2:1 mixture of 2- (bromomethyl)-4-chloro-1-iodobenzene and 1-bromo-2-(bromomethyl)-4- chlorobenzene (1.99 g).The faster running material (2.07 g) was combined with the triturated material (1.30 g) and was re-purified on 50 g silica SPE eluting with cyclohexane, exactly as before. A second batch of the title compounds, again as a 2:1 of 2-(bromomethyl)-4-chloro-1- iodobenzene and 1-bromo-2-(bromomethyl)-4-chlorobenzene (2.38 g) was obtained; LCMS: (System 2) tRET = 1 -37 min (no ions detected).; Intermediate 7: 1 -r(5-Chloro-2-iodophenyl)methyl1-Lambda/-(2,6-difluorophenyl)-1 H- pyrazole-3-carboxamide/V-(2,6-difluorophenyl)-1 H-pyrazole-3-carboxamide (350 mg, 1.57 mmol), 2:1 Mixture of 2-(bromomethyl)-4-chloro-1-iodobenzene and 1-bromo-2-(bromomethyl)-4- chlorobenzene (495 mg, 1.57 mmol) and potassium carbonate (433 mg, 3.14 mmol) were weighed into a flask. DMF (15 ml) was then added and the reaction was stirred at ambient temperature under nitrogen.After 16 h, the reaction mixture was partitioned between DCM (100 ml) and water (100 ml). The layers were separated and the aqueous layer extracted with further DCM (50 ml). The combined DCM extracts were dried (sodium sulfate) and evaporated to give a crude product as an oil. This product was re-dissolved in DCM and loaded on to 50 g silica SPE which had been pre-equilibrated with cyclohexane. The product was then purified using 0-50% ethyl acetate-cyclohexane gradient to give a white solid (2:1 mixture of iodide and bromide).200 mg of the product mixture was purified by MDAP (2 x 100 mg batches). Each sample was dissolved in 1 :1 MeOH:DMSO (1 ml) and purified (supelcosil ABZ+Plus column) (Method A) eluting with solvents A/B (A: Water + 0.1% Formic acid, B: MeCN:Water 95:5 + 0.05% Formic acid).The first eluted product from each run was combined and partitioned between NaHCO3 (aq) and DCM. The layers were separated and the aqueous layer was extracted with a second portion of DCM. The DCM extract was dried (Na2SO4) and evaporated to give 1-[(2-bromo-5-chlorophenyl)methyl]-Lambda/-(2,6-difluorophenyl)-1 H- pyrazole-3-carboxamide as a colourless oil, 45 mg; LCMS: (System 2) MH+= 426, 428 and 430 (Cl, Br isotopes), tRET = 1.22 min.The second eluted product from each run was combined and partitioned betweenNaHCO3 (aq) and DCM. The layers were separated and the aqueous layer was extracted with a second portion of DCM. The DCM extract was dried (Na2SO4) and evaporated to give the title compound as a colourless oil (121 mg); LCMS: (System2) MH+= 474 and 476 (Cl isotopes) tRET = 1 -25 min.
Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 23399-70-4.
Reference:
Patent; GLAXO GROUP LIMITED; COE, Diane, Mary; COOPER, Anthony, William, James; GORE, Paul, Martin; HOUSE, David; SENGER, Stefan; VILE, Sadie; WO2010/122088; (2010); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com