Ethanone,1-(6-quinoxalinyl)-(9CI)

To a solution of Compound 2 (1 g, 4.6 mmol) in dry THF (10 mL) at 0 °C under N2 was added MeMgBr (2 mL, 3.0 mol/L, 6 mmol) dropwise. The resulting solution was slowly warm to RT over 2 hours. The mixture was diluted with NH4C1 solution and extracted with EA. The organic extracts were concentrated to give a crude oil. The crude product was purified by silica gel chromatography to afford Compound 3 (600 mg, 75.7 percent).A mixture of quinoxaline-6-carboxylic acid (2 g, 11.49 mmol) and thionyl chloride (30 mL) was stirred at reflux for 2 hours. The reaction mixture was concentrated to dryness using a rotary evaporator to afford quinoxaline-6- EPO To a solution of Compound 2 (1 g, 4.6 mmol) in dry THF (10 mL) at 0 °C under N2 was added MeMgBr (2 mL, 3.0 mol/L, 6 mmol) dropwise. The resulting solution was slowly warm to RT over 2 hours. The mixture was diluted with NH4C1 solution and extracted with EA. The organic extracts were concentrated to give a crude oil. The crude product was purified by silica gel chromatography to afford Compound 3 (600 mg, 75.7 percent).A mixture of quinoxaline-6-carboxylic acid (2 g, 11.49 mmol) and thionyl chloride (30 mL) was stirred at reflux for 2 hours. The reaction mixture was concentrated to dryness using a rotary evaporator to afford quinoxaline-6- EPO To a degassed stirred solution of 6-bromo quinoxaline (2.0 g, 9.50 mmol) in toluene (20 mL), 1- ethoxy vinyl tributyltin (3.8 g, 10.5 mmol) followed by Pd(PPhAfter dissolving 6-(quinoxalin-6-yl)ethan-1-one (4.6 g, 27.0 mmol) synthesized in Step 1 and diethyl oxalate (7.3 mL, 53.9 mmol) in ethanol (9 mL), a 2 M ethoxysodium solution (26.9 mL, 53.9 mmol) was slowly added dropwise thereto at 50C, and the result was refluxed for 2 hours. After cooling the result to room temperature, the solvent was vacuum concentrated, and the result was acidified by adding 2 M HCl dropwise thereto. Dichloromethane was introduced thereto for extraction, and the organic layer was dried using anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and purified using column chromatography to obtain a target compound (6.7 g). 1H NMR spectrum (300 MHz, CDCl3) delta 8.96(s, 2H), 8.78(s, 1H), 8.35(dd, 1H), 8.24(d, 1H), 7.27(s, 1H), 4.44(q, 2H), 1.45(t, 3H).After adding 6-bromoquinoxaline (3.8 g, 18.2 mmol), n-butyl vinyl ether (12.3 mL, 95.2 mmol), potassium carbonate (3.1 g, 22.8 mmol), 1, 3-bis(diphenylphosphino)propane (504 mg, 1.3 mmol) and palladium(II) acetate (124 mg, 0.5 mmol) to N, N-dimethylformamide (47 mL) and water (6 mL), the result was stirred and refluxed for 6 hours. After terminating the reaction, the result was cooled to room temperature, 2 N hydrochloric acid was added thereto, and the result was stirred for 0.5 hours. Ethyl acetate was added thereto, the organic layer was washed with water and sodium bicarbonate, dried using anhydrous magnesium sulfate, and filtered. The filtrate was concentrated and purified using column chromatography to obtain a target compound (2.4 g). 1H NMR spectrum (300 MHz, DMSO-d6) delta 10.05(d, 1H), 9.73(t, 1H), 8.71(s, 1H), 7.97(d, 1H), 3.16(s, 3H).To a degassed stirred solution of 6-bromo quinoxaline (2.0 g, 9.50 mmol) in toluene (20 mL), 1- ethoxy vinyl tributyltin (3.8 g, 10.5 mmol) followed by Pd(PPh3)2CI2 (0.67 g, 0.95 mmol) were added at RT and stirred at 90 C overnight. After completion of the reaction (monitored by TLC), the reaction mixture was cooled to RT, filtered through celite and the obtained filtrate was evaporated under vacuum. To the resulting crude mixture, 6 N HCI solution (20 mL) was added and the mixture was stirred at RT for 1 h. The solution was neutralized with sat. NaHC03 and the aqueous layer was extracted with DCM (2 x 100 mL). The combined organic layer was dried over Na2S04 and concentrated under vacuum. The resulting crude material was purified by flash chromatography (Biotage Isolera, eluent: 30% EtOAc in hexane) to afford the title compound. Yield: 45% (800 mg, brown solid). 1H NMR (400 MHz, DMSO-tf6): delta 9.06-9.04 (m, 2H), 8.70 (d, J = 2.4 Hz, 1 H), 8.28 (dd, J = 8.8, 2.8 Hz, 1 H), 8.16 (d, J = 8.4 Hz, 1 H), 2.97 (s, 3H). LCMS: (Method A) 173 (M+H), Rt. 2.2 min, 99.1 % (Max).Titanium tetraisopropoxide (0.08 mL, 0.27 mmol) was added to a stirred suspension of Intermediate 3b (57 mg, 0.25 mmol) and l-(quinoxalin-6-yl)ethanone (CAS: 83570-42- 7; 50 mg, 0.29 mmol) in THF (1.5 mL) at rt and under N2 atmosphere. The mixture was stirred into a sealed tube at 80 C for 16 h. Then sodium cyanoborohydride (28 mg, 0.45 mmol) was added and the mixture was further stirred at 80 C for 16 h. Then, NaHC03 (aq. sat. soltn.) and DCM were added to the mixture. The solvent was evaporated in vacuo and the crude product was purified by flash column (0323) chromatography (silica gel, 7N solution of NH3 in MeOH in DCM, from 0/100 to 10/90) and then by RP HPLC (Stationary phase: C18 XBridge 30 x 100 mm 5 muetaiota; mobile phase: gradient from 81 % 1 OmM NH4CO3H pH 9 solution in water, 19% (0324) CH3CN to 64% lOmM NH4CO3H pH 9 solution in water, 36% CH3CN). The desired fractions were collected and concentrated in vacuo to yield product 7 (10 mg, 10%> yield) as yellow oil.Titanium tetraisopropoxide (0.1 mL, 0.34 mmol) was added to a stirred suspension of Intermediate 3a (71 mg, 0.31 mmol) and l-(quinoxalin-6-yl)ethanone (CAS: 83570-42- 7; 63 mg, 0.37 mmol) in THF (1.5 mL) at rt and under N2 atmosphere. The mixture was stirred into a sealed tube at 80 C for 16 h. Then sodium cyanoborohydride (30 mg, 0.48 mmol) was added and the mixture was further stirred at 80 C for 16 h. Then, NaHC03 (aq. sat. soltn.) and DCM were added to the mixture. The solvent was evaporated in vacuo and the crude product was purified by flash column (0320) chromatography (silica gel, 7N solution of NH3 in MeOH in DCM, from 0/100 to 10/90) and then by RP HPLC (Stationary phase: CI 8 XBridge 30 x 100 mm 5 muetaiota; mobile phase: gradient from 81% lOmM NH4CO3H pH 9 solution in water, 19% CH3CN to 64% lOmM NH4CO3H pH 9 solution in water, 36% CH3CN). The desired fractions were collected and concentrated in vacuo to yield product 6 (15 mg, 13% yield) as yellow oil.

Molecular Weight:172.18
XLogP3:1.2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:172.063662883
Monoisotopic Mass:172.063662883
Topological Polar Surface Area:42.8
Heavy Atom Count:13
Complexity:205
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes