4-Chloro-3-quinolinecarboxaldehyde

A formylation mixture was prepared from 41.2 mL (444.4 mmol, 6.00 mol eq) of POCl3 that was added dropwise to 90.0 mL of DMF (abs) at 0 C. Resulted solution was stirred for 15 min under Ar at rt. Then 9.0 mL (74.0 mmol, 1.00 mol eq) of 1-(2-aminophenyl)ethanone was added dropwise to the stirred formylation mixture within 30 min and the mixture heated to 60 C for 16 h (instead of 4 h, described previously in the literature) (Seixas et al. 2011). Then, the mixture was cooled to rt by adding 400 g of crashed ice in 200 mL H2O and the reaction neutralized to pH 7 by solid NaHCO3. Precipitated yellow product was filtered off, dissolved in CHCl3, extracted with water. A separated organic layer was dried over Na2SO4, filtered, concentrated by RVO and HV. Crystallization from EA with charcoal bleaching provided 8.50 g (44.4 mmol, 60%) of General procedure: POCl3 (16.1 g, 0.105 mol) was added dropwise to DMF (10 mL) at 0 C, and the resulting mixture was stirred for 15 min under N2 at r.t. A solution of the appropriate 1-(2-aminophenyl)ethanone 1 (15.0mmol) in DMF (10 mL) was added dropwise from a syringe, and the mixture was heated at 90 C for 12 h. After it had been cooled to r.t., the mixture was distilled to remove excess POCl3. The viscous oily residue was slowly added to crushed ice, and the mixture was neutralized with sat. aq NaHCO3. The product was extracted with CHCl3 (2 × 50 mL) and the combined organic phases were washed with water, dried (MgSO4), filtered, and concentrated. The residue was driedin vacuo to give a crude product that was purified by column chromatography(silica gel).To a 00C solution of l-(2-aminophenyl)ethan-l-one (2.0 g, 14.8 mmol) in anhydrous DMF (10 mL) was added dropwise phosphorus oxychloride (5.5 mL, 59.2 mmol). The reaction mixture was stirred at room temperature for 1 hour and at 900C for 3 hours. After cooling to room temperature, the mixture was poured in a mixture of ice/water/NH4OAc to neutralize. The mixture was stirred at room temperature overnight. The product was recovered by filtration and washed with water (2 x 20 mL). The solid material was dissolved in ethyl acetate (100 mL). The solution was dried over MgSO4, filtered, evaporated, and dried in vacuo, affording 4- chloroquinoline-3-carbaldehyde (1.2 g, 43% yield). The product was used without further purification.General procedure: (E)-3-styrylquinolin-4(1H)-ones 1a-1k and 1t were prepared according to theliterature procedure (Scheme 1).1, 2 POCl3 (123.4 mmol) was added dropwise to 25mL dry N, N-dimethylformamide (DMF) at 0 C under argon, and the mixture wasstirred for 15 min at room temperature. Then a solution of 3 1-(2-aminophenyl)ethanones (20.6 mmol) in dry DMF (3 mL) was added dropwise. The reactionsolution was heated to 60 C and stirred for 4 h. The reaction was stopped by pouredinto 100 g ice and 100 mL water, and neutralized with NaHCO3. The formed solid wasfiltered off, dissolved into 200 mL CH2Cl2 and washed with 3 × 200 mL water. Theorganic layer was dried over Na2SO4 and concentrated under reduced pressure. Theresulting solid was purified by column chromatography on silica gel (petroleum ether:ethyl acetate = 20:1-10:1) to afford To an anh. DMF (20 ml_), POCI3 (8.27 ml_, 88.8 mmol, 6 eq) was added dropwise at 0C. Then 1-(2-aminophenyl)ethan-1-one (2.00 g, 14.8 mmol, 1 eq) in anh. DMF (5 ml.) was added drop- wise, and the reaction was heated for 4 h at 60C. Afterwards, the reactions was cooled down to 0C, quenched with water. Then solution was neutralized with saturated NaHCC>3 aqueous solution, diluted in water and extracted with DCM. The layers were separated. Organic layer was dried over MgS04, filtered off and concentrated in vacuo to afford the title compound (1.43 g, 7.49 mmol, yield 51 %) as an orange solid that was taken to the next step without additional purification. ESI-MS: 192 [M+H]+General procedure: A mixture of sodium hydride (6.0 mmol) and appropriate phosphonium halide(6.0 mmol) in 50 mL dry THF was refluxed 3 h (R2 = H, Me, F, Cl) or 1 h (R2 = OEt)under argon. When the solution turned into orange, and the suspension of thephosphonium salt disappeared, it indicated that ylide was formed. Subsequently,

Molecular Weight:191.61
XLogP3:2.3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:191.0137915
Monoisotopic Mass:191.0137915
Topological Polar Surface Area:30
Heavy Atom Count:13
Complexity:197
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes