6,7-Dimethoxy-4-hydroxyquinoline

Ethyl 4-hydroxy-6, 7-dimethoxyquinoline-3-carboxylate (700 mg, 2.53 mmol) was added into a solution of potassium hydroxide (450 mg, 7.6 mmol) in 20 mL of H20/EtOH (1: 1; v: v). This mixture was placed in a sealed vessel (XP-500 Plus vessel) and heated by microwave (MARS 5 Microwave System) at 180°C, under 260-280 psi pressure for 50 minutes. The reaction mixture was cooled to room temperature and transferred into a flask. The solution was then acidified with HOAc (about 2 mL) to pH about 6, saturated with NaCl and extracted with THF (3 x 100 mL). The combined oil layers were washed with brine and concentrated to give 6, 7-dimethoxyquinolin-4-ol (90percent yield); (at) H NMR (400 MHz, DMSO-a\3) 6 ppm 3.81 (s, 3 H) 3.84 (s, 3 H) 5.93 (d, J--7.3 Hz, 1 H) 7.05 (s, 1 H) 7.42 (s, 1 H) 7.76 (d, (at)=7.3 Hz, 1 H).To a solution of 2-amino-4, 5-dimethoxylacetophenone (4.5 g, 23 mmol) in DME (100 ml_) was added NaOMe (5.0 g, 92 mmol). The reaction was stirred for 30 min after which ethyl formate (8.5 g, 115 mmol) was added and the reaction mixture was stirred for 16 h at rt. Then NaOEt (21percent dispersion in oil, 22 g, 69.1 mmol) was 5-((3, 4-Dimethoxyphenylamino)methylene)-2, 2-dimethyl-1, 3-dioxane-4, 6-dione (16.1 g, 52 mmol) was added to a pre-heated 1000 mL round-bottom flask containing 1-phenoxy benzene (100 mL) at 230 °C. [0169] A solution of 5-(((3, 4-dimethoxyphenyl)amino)methylene)-2, 2-dimethyl- l, 3-dioxane-4, 6-dione (100 g, 0.33 mol) in 1, 2-dichlorobenzene (1.2 L, Aladdin) was heated to reflux for 5 hours, then cooled down to -20 °C and stirred further for 2 hours. The mixture was filtered to give the title compound as a pale solid (45.8 g, 68.6percent). MS (ESI, pos. ion) m/z: 206.1 [M+H]To a dry IL RBF containing 6, 7-dimethoxy-quinolin-4-ol (20.9 g, 102 mmol), which can be prepared according to the procedure of Riegel, B. (J. Amer. Chem. Soc. 1946, 68, 1264), was added DCM (500 niL), 4-dimethylaminopyridine (1.24 g, 10 mmol) and 2, 6-lutidine (24 mL, 204 mmol). The mixture was vigorously stirred at RT. Trifluoromethanesulfonyl chloride (14 mL, 132 mmol) was added dropwise to the solution. After addition was complete, the mixture was stirred ice bath for 2 to 3 hrs. On LC/MS indicating the reaction completion, the reaction mixture was concentrated in vacuo and placed under high vacuum to remove residual 2, 6-lutidine. To the resulting brown solids was added methanol (250 mL). The resulting slurry was stirred for 30 min before adding water (1 L). The solids were isolated by filtration, followed by a water wash. The resulting solid was dried under high vacuum overnight yielding trifluoromethanesulfonic acid 6, 7-dimethoxy-quinolin-4-yl ester as a light brown solid (27 g, 80%). 1H NMR (400MHz, DMSO, d6): delta 8.82 (d, IH), 7.59 (m, 2H), 7.20 (s, IH), 3.97 (d, 6H). LC/MS: M+H - 338.

Molecular Weight:205.21
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:205.07389321
Monoisotopic Mass:205.07389321
Topological Polar Surface Area:47.6
Heavy Atom Count:15
Complexity:277
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes