3-Morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one

At room temperature 100 g (0.60 µM) intermediate (2) dissolved in 400 ml 1, 4 - dioxane, adding 60 ml (0.66 µM) morpholine and 210 ml (1.50 µM) triethylamine. Raising the temperature to 110 °C. TLC detection 4.5 h reaction finishes, cooling to room temperature, still precipitate solid. Filtered, and the filtrate is distilled under reduced pressure to, the evaporation to get the yellow solid, washing with ethyl ether (2 × 400 ml), washed with water (2 × 200 ml), dried to obtain the white solid powder 100.5 g (theoretical yield is 108.5 g), yield is 92percent.Morpholine (14 cm3) and 7 g 10 (0.0417 mol) werecharged into a 50 cm3 single neck round-bottomed flask, equipped with a stir bar, a condenser, and a CaCl2 guardtube. The resulting mixture was refluxed for 2 h, cooled toRT, and poured into 50 cm3 ice cold water. The product was extracted with dichloromethane (3 9 40 cm3). Theorganic layers were combined, washed with 30 cm3 water and 30 cm3 brine, dried over Na2SO4, and concentrated under reduced pressure at<45 °C. The crude material thus obtained was stirred with 15 cm3 MTBE at RT for 10 min, filtered, washed with 10 cm3 n-hexane, and dried at RT for 4 h to obtain 12 (5.6 g, 74percent, 95.3percent purity by HPLC analysis) as a dark brown solid. 1H NMR spectral data of 12 (see Supplementary Material for details) was inagreement with that reported in Ref. [14].The 3, 3-dichloro-piperidine-2-one (22.0g, 131 . 7mmol) dissolved in morpholine (80 ml) in. Then heating to 140 °C stirring 12 hours. Cooling to room temperature, solvent evaporate under reduced pressure. The crude product after column chromatography purification (dichloromethane/methanol (v/v)=20/1), get white solid (13g, 55percent).3, 3-dichloropiperidin-2-one (22.0g, 131.7mmol) It was dissolved in morpholine (80mL) then stirred and heated to 140°C for 12 hours. Cooled to room temperature, the solvent was evaporated under reduced pressure. The crude product was purified by column chromatography (dichloromethane / methanol (v / v) = 20/1) giving a white solid (13g, 55percent).The 3, 3- [...] -2-one (22.0g, 131 . 7mmol) dissolved in morpholine (80 ml) in. Then heating to 140 °C stirring 12 hours. Cooling to room temperature, solvent evaporate under reduced pressure. The crude product after column chromatography purification (dichloromethane/methanol (v/v)=20/1), get white solid (13g, 55percent).The 3, 3-dichloropiperidine 2-one(22.0g, 131.7mmol) was dissolved in morpholine (80mL) in.Then heated to 140 stirred for 12 hours.Cooled to room temperature, the solvent was distilled off under reduced pressure.The crude product was purified by column chromatography (dichloromethane / methanol (v / v) = 20/1), as a white solid (13g, 55percent).The 3, 3-dichloro-2-one (22.0g, 131.7mmol) was dissolved in morpholine (80mL) in. Then heated to 140 stirred for 12 hours. Cooled to room temperature, the solvent was distilled off under reduced pressure. The crude product was purified by column chromatography (dichloromethane / methanol (v / v) = 20/1), as a white solid (13g, 55percent).A solution of 3, 3-dichloropiperidin-2-one (22.Og, 131.7 mmol)Dissolved in morpholine(80 mL).Then heated toThe mixture was stirred at 140 ° C for 12 hours. Cool to room temperature and evaporate the solvent under reduced pressure. The crude product was purified by column chromatography (dichloromethane / methanol (v /Ν) = 20/1) to give a white solid (13 g, 55percent).3, 3-dichloropiperidin-2-one (22. 0 g, 131.7 mmol) was dissolved in morpholine (80 mL).And then heated to 140 ° C for 12 hours.Cool to room temperature and evaporate the solvent under reduced pressure. The crude product was purified by column chromatography (dichloromethane / methanol (v / v = 20/1) to give a white solid (13 g, 55percent).3-Morpholine-5, 6-dihydropyridine-2 (1 H) -one[0145] 3, 3-Dichloropiperidin-2-one (22. 0 g, 131.7 mmol) was dissolved in morpholine (80 mL). And then heated to 140 ° C for 12 hours. Cool to room temperature and evaporate the solvent under reduced pressure. The crude product was purified by column chromatography (dichloromethane / methanol (v / v = 20/1) to give a white solid (13 g, 55percent).3, 3-dichloropiperidin-2-one (22.0 g, 131.7 mmol) was dissolved in morpholine (80 mL).Followed by heating to 140 ° C for 12 hours.Cool to room temperature and evaporate the solvent under reduced pressure.The crude product was purified by column chromatography (dichloromethane / methanol (v / v) = 20/1) to give a white solid (13 g, 55percent).Step B: A solution of 3 (1.3 g, 100.0 mmol) and morpholine in DMF (5 mL) was treated with Li1.3 g of 3-chloro-5, 6-dihydro-2(1H)-pyridone and 0.9 g of morpholine were dissolved in 5 mL of DMF, 1.5 grams of anhydrous lithium carbonate was added, heated to 130 degrees, and reacted for 3 hours.. The reaction mixture was filtered, distilled under reduced pressure to remove the solvent and the residue was purified by column chromatography to give 0.6 g of a white solid, yield 30.2percent.

Molecular Weight:182.22
XLogP3:0.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:182.105527694
Monoisotopic Mass:182.105527694
Topological Polar Surface Area:41.6
Heavy Atom Count:13
Complexity:232
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes