6-Iodoquinoline

Sodium iodide (4.32 g, 28.8 mmol), Copper (I) iodide (137 mg, 0.72 mmol) and N, N'-Dimethyl-cyclohexane-l, 2-diamine (0.227 mL, 1.44 mmol) and 6- Bromoquinoline (3g, 14.4 mmol) in dioxane (15 mL) were charged in a 25 mL microwave tube. The tube was flushed with Nitrogen and sealed with a Teflon septum Intermediate M 6-[(6-chloro-[1 , 2, 4]triazolo[4, 3-b]pyridazin-3-yl)-difluoro-methyl]-quinoline NSodium iodide (4.32 g, 28.8 mmol), copper (I) iodide (137 mg, 0.72 mmol), 6-bromo- quinoline (3 g, 14.4 mmol), N, N'-dimethyl-cyclohexane (0.227 ml_, 1 .44 mmol) and dioxane were charged in a microwave tube (25 ml_). The tube was purged with nitrogen for 10 min and sealed with a Teflon septum. The reaction mixture was stirred at 1 10 Step 1 : 6-iodoquinoline6-bromoquinoline (80, 1 g, 0, 385 mol) is dissolved in n-butanol (0.8 L). Copper catalyst CuI (3, 7 g, 0, 019 mol), a copper-ligand N, N'-dimethylethylenediamine (3.4 g, 0, 0385 mol) and an iodide source NaI (115, 5 g, 0, 770 mol) are added and the mixture is heated in a heating jacket, under inert atmosphere to 1206-bromoquinoline (10.4 g, 50.0 mmol), CuI (0.476 g, 2.5 mmol) NaI (15.0 g, 100.0 mmol) and DMEDA (0.5 mL, 5.0 mmol) Add 100mL dioxane, N2 protection, 140 for sealing reaction 24h LC-MS detection, the reaction is complete. After cooling, the filtrate was washed with saturated NaCl solution, Na2SO4, filtered, concentrated, and chromatographed to give 6-iodoquinoline as a yellow solid (12.5 g).General procedure: To a solution of hexane (5 mL), DMSO (0.5 mL), and trifluoromethanesulfonicacid (0.54 mL, 6 mmol) at 5 °C were sequentially added thequinoline amine 4b or 4c (2 mmol) and NaNO2 (350 mg, 5 mmol) understirring, and the mixture was stirred for 10 min. The resultingmixture was then stirred for 50 min at r.t. until the starting aminehad been consumed as monitored by TLC. An emission of N2 bubbleswas not observed and the reaction solution gave the positive probeon diazonium salts with β-naphthol. Next, KI (2.4 mmol) in H2O (0.5mL) was added and the mixture was stirred 10 min at r.t. until evolutionof N2 bubbles ceased. In the case of 4b, the solid 3-iodoquinoline6 obtained was filtered, washed with H2O, and dried. In the case of 3c, the reaction mixture was poured into H2O and the oily product 7 was extracted with EtOAc (2 × 25 mL). The combined organic extractswere dried (Na2SO4), filtered, and the solvent was removed under reducedpressure on a rotary evaporator. The product 7 was purified bysilica gel flash chromatography (eluent: CH2Cl2).General procedure: A 1N HCl solution (82.5 mL) was added to the aniline (~1 mmol) in a round bottom flask. To this was added acrolein diethyl acetal (2.5 mmol). The resulting solution was refluxed at 111 °C for 24 hours. After cooling to room temperature, the solution was neutralized (pH 7−8) by addition of solid Na2CO3. The product was then extracted into dichloromethane (3 x 100 mL), and the combined organic layers were dried over Na2SO4 and evaporated under reduced pressure. The crude residue was then purified by column chromatography (elution mixture of hexane with ethyl acetate or 15percent ethyl acetate/cyclohexane with methanol) to give the desired quinoline product.

Molecular Weight:255.05
XLogP3:2.9
Hydrogen Bond Acceptor Count:1
Exact Mass:254.95450
Monoisotopic Mass:254.95450
Topological Polar Surface Area:12.9
Heavy Atom Count:11
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes