1,2-Bis(1,1-dimethylethyl) (2S)-4-oxo-1,2-pyrrolidinedicarboxylate

To synthesize intermediate compound 16c, a solution of intermediate compound 16b (1.35 g, 5.9 mmol) in anhydrous CH2CI2 (27 mL) is cooled to 0 °C. tert- Butyl alcohol (1 .7 mL, 17.7 mmol) and DMAP (72 mg, 0.59 mmol) are added to the solution. After stirring for 5 min, 1 -ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1 .19 g, 6.2 mmol) is added to the solution. The reaction is allowed to warm to room temperature and stirred overnight. The mixture is quenched by saturated NaHCOEXAMPLE 5 STR11 Step A: 1-(tert-Butyloxycarbonyl)-4-oxo-L-Proline tert-Butyl Ester The difference from is that Step 3 specifically includes the synthesis of Compound 4:1 equivalent of compound 3 and a third organic solvent are sequentially added to the reactor, the third organic solvent is methyl tert-butyl ether, and the weight of the third organic solvent is 6 times that of compound 3, and mechanical stirring is started.0.4 equivalent of 4-dimethylaminopyridine was added, and then a solution dissolved in a third organic solvent and containing 1.1 equivalents of Boc anhydride was added dropwise.The weight of the third organic solvent is twice that of the compound 3. After the addition, the mixture is heated to reflux for 3 hours, and 60 g of water is added to the reaction flask.The layers were separated and concentrated to a liquid-free liquid to give a brown-yellow oil, which was recrystallized from n-heptane to afford compound 4.D20 (10 mL) and prewashed (with D20) silica gel (4 g) were added to a solution of (5)-di- tert-butyl 4-oxopyrrolidine-l , 2-dicarboxylate (4.0 g, 14 mmol) in dry THF (10 mL). After the reaction mixture was stirred at room temperature for 8 days, the silica gel was removed by filtration. The filtrate was extracted with ethyl acetate and the organic phase was concentrated to give (i?)-[3, 3-2H2]-4-oxo-pyrrolidine-l , 2-dicarboxylic acid di-tert-butyl ester (Compound P) as a light yellow oil (4.0 g). 1H NMR (CDCl3-d, 400 MHz): delta ppm 4.55-4.70 (m, 1H), 3.82-3.92 (m, 2H), 1.49 (s, 9H), 1.48 (s, 9H).(2) 17.36 g of the compound hydrazine was dissolved in dichloromethane, and 9.45 g of N-methyl_N_oxidized morpholine was added and stirred at room temperature for 1.5 hours, and the reaction completely gave a black turbid liquid, and the reaction solution was filtered off to remove insoluble matter. The filtrate was evaporated to dryness and purified by column chromatography to yield 16.75 g of white solid compound m, yield 92.74%(3) 16.75 g of compound 1 hydrazine was dissolved in dichloromethane, and 15.52 g of 1-(3-methyl-1-phenyl-7-pyrazolyl)piperazine (Compound IV) and 2.8 mL of acetic acid were added, and finally ice 25.85 g of sodium triacetoxyborohydride was added under the bath, and the reaction was completed after stirring at room temperature for 24 hours to obtain a brownish yellow solution. The reaction solution was slowly poured into 200 mL of sodium hydrogencarbonate solution, extracted with dichloromethane, and washed with water. , drying, column chromatography purification to obtain 22.20 g of white solid compound V, the yield was 80.90%