4-methyl-3-oxo-N-phenyl pentanamide

To a 1000 ml dry-dried reaction flask, 60 g (0.416 mol) of methyl isobutyrylacetate was successively charged, 120 g (1.288 mol) of aniline, 6g 4-dimethylaminopyridine.Open slowly stirring, Heated to an internal temperature of 100 ° C, Incubated for 16 hours.The fractionator is fractionated to produce the reacted methanol.After the reaction, 70 ° C under reduced pressure to recover aniline, 74.7 g of aniline was recovered, Aniline recovery rate of 92percent; get concentrated 100G, And then at this temperature by adding water kg, Cooling to 30 ° C stirring crystallization for 5 hours or more, filtration, water rinse filter cake 3 times, the cake dried product was 82.3g, HPLC analysis of 99.8percent, the yield of 96.4percentEXAMPLE-9; 4-Methyl-3-oxo-N-phenyl pentanamide; Methyl isobutyryl acetate (lOOg, 0.693 mol) is placed in a 4 neck RB flask equipped with a stirring rod, thermometer socket and a distillation condenser. Aniline (71 g, 0.762 mol) and triethylamine (15g, 0.148 mol) are added and the contents are heated to 80-85°C under agitation. The contents are maintained at 80-85°C for lhr and the temperature is gradually raised to 120-125°C. The reaction is maintained for 4-6 hours, during which period methanol formed in the reaction is collected (48 ml). The reaction is continued till methanol no longer distills out . the contents are cooled to 25-30°C. The reaction mixture is quenched with 2N hydrochloric acid (200ml) and extracted with methylene chloride (100ml). The aqueous layer is extracted twice with methylene chloride (2 xlOO ml). The combined methylene chloride extract (300 ml) is sequentially washed with IN hydrochloric acid (50ml), 5percent aqueous sodium bicarbonate (50 ml) and 5percent aq. sodium chloride (50 ml). The organic layer is concentrated to remove methylene chloride on a water bath at 50-55°C, traces of methlyene chloride are finally removed under vacuum. 4-Methyl-3-oxo-N-phenyl pentanamide (132 g, 92.7percent, HPLC purity 98.85percent) thus obtained is used in next step as such.A mixture of compound 2 (5.00 g, 34.69 mmol), triethylamine(0.88 g, 8.70 mmol), and aniline (3.88 g, 41.62 mmol) in toluene (30 mL)was heated to 70 °C. The reaction mixture was stirred at 70 °C for 1 h and then gradually heated to 110–120 °C. The methanol formed during the reaction was distilled off together with some toluene for 5 h. After cooling to room temperature, the mixture was washed with 5 percent hydrochloric acid (30 mL) and water(2×30 mL). The organic phases were dried over anhydrous magnesium sulfate and then concentrated to give a red oil 3 (6.55 g, 91.9 percent yield). 1H NMR (600 MHz, CDCl3) δ: 9.23 (s, 1H), 7.09–7.55 (m, 5H), 3.59 (s, 2H), 2.73(m, 1H), 1.17(d, J6.6 Hz, 6H). 13C NMR (150 MHz, CDCl3) δ: 210.4, 164.5, 137.6, 128.8, 124.5, 120.1, 47.7, 41.5, 17.6.The first intermediate prepared in the step (1) is subjected to a substitution reaction with the aniline under the action of the second catalyst, 2-Methyl-3, 5-dicarbonyl-5-anilino-butane (second intermediate) is obtained; the reaction scheme is as follows: A reaction flask with a thermometer and a stirrer in a 500 mL format is used as a reaction vessel.Adding the first intermediate 2-methyl-3-carbonyl-pentanoic acid methyl ester 30 g (0.2 mol), aniline 22.5 g (0.24 mol), adding solvent xylene 200 mL, 2.5 g (0.04 mol) of a catalyst ethylenediamine was added, and the reaction was heated to a temperature of about 140 to 150 ° C under a nitrogen atmosphere.After the methanol formed is distilled off, the reflux reaction is continued for about 4 hours, and the TLC detection of the raw material reaction is complete; After the reaction is completed, it is cooled to room temperature, adjusted to neutral with dilute hydrochloric acid, stirred, Filtration, washing with 100 mL of a saturated sodium chloride solution, and separating the organic phase to remove xylene under reduced pressure.Further, acetone was added to carry out recrystallization to obtain white purified solid 2-methyl-3, 5-dicarbonyl-5-anilino-butane (37 g).10 g of ethylisobutyrylacetate (63.2 mmol) was dissolved in 30 ml of toluene, and6.5 g of aniline (70 mmol) was added to the resulting mixture and refluxed for 3 hours. When the reaction was completed, 50 ml of IN HCl was added to the resulting reaction mixture, and stirred to separate an organic phase. The organic phase was diluted with 50 ml of ethylacetate, washed with distilled water and saturated saline, and then concentrated under a reduced pressure to obtain brown oil. The resultant brown oil was washed with nucleic acid to obtain 10.5 g of brown oil (Yield: 81percent).[92] IH-NMR (CDC13)δ: 1.14 (d, 6H), 2.71 (m, IH), 3.58 (s, 2H), 7.09 (m, IH), 7.24-7.31 (m, 2H), 7.53 (d, 2H), 9.20 (b, IH)[93] Mass (M+l): 206EXAMPLE 19.1 The compound 1 (50.0 g), aniline (38.8 g), triethylamine (8.8 g) is added to the toluene (300 ml) in, heating to 85 °C, reaction 1 hour, the reaction system is heated up to reflux 4 hours. TLC (PE:EA=4:1) display the completion of reaction, the reaction system after cooling to room temperature, adding ethyl acetate (500 ml), respectively water (100 ml) washing, 5percent hydrochloric acid aqueous solution (150 ml) washing, saturated salt water washing 3 times after drying, turns on lathe does to obtain compound 2 (67.0 g).

Molecular Weight:205.25
XLogP3:2.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:4
Exact Mass:205.110278721
Monoisotopic Mass:205.110278721
Topological Polar Surface Area:46.2
Heavy Atom Count:15
Complexity:230
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes