2-CHLORO-3-NITRO-5-(TRIFLUOROMETHYL)PYRIDINE

(2) 52g of compound 2 was added to 150ml of phosphorus oxychloride, With stirring slowly add 21g of quinoline, Control feeding speed, So that the internal temperature does not exceed 50 degrees, At the same time compound 2 slowly dissolved, Argon gas protection system, oil bath heating, Set the external temperature 120 degrees, 20-30 minutes after the system began to reflow, Maintain the system slightly boiled for 1.5 hours.TLC showed the reaction of raw materials is completed, stop heating, The system was concentrated under reduced pressure to remove phosphorus oxychloride, then dissolved in EA (400 ml) and the quinoline was removed by washing with 2N HCl (200 ml * 2)The mixture was washed with saturated sodium bicarbonate solution to neutrality and the organic phase was dried to give compound 3.TLC information: Raw material Rf = 0.1, Product Rf = 0.7. Developing agent: PE / EA / = 15/1.Measured product 50 grams, brown oil, yield 88percent2-Hydroxy-3-nitro-5-trifluoromethylpyridine (7.4 g, 35.6 mmol) was suspended in phosphorous oxy chloride (15 ml, 164 mmol) and quinoline (5 ml, 42 mmol) (CAUTION: Exothermic) and re fluxed for 18 hours. The reaction was cooled to room temperature, poured on ice (100 g) and neutralized with NaHCO(+/-)-9-[Acetyl-(3, 5-bis-trifluoromethyl-benzyl)amino]-2-methyl-3-trifluoromethyl- 6, 7, 8, 9-tetrahydro-pyrido[3, 2-b]azepine-5-carboxylic acid isopropyl ester; Step 1;. Preparation of 2-Chloro-3-nitro-5-trifluoromethyl-pyridine; Add 3-nitro-5-trifluoromethyl-pyridin-2-ol (10.0 g, 48 mmol) to a mixture of phosphorous oxychloride (27 mL) and dimethylformamide (1.5 mL). Heat the resulting mixture at 110 °C for 30 min. Cool the reaction mixture to room temperature and pour onto ice-water. Add sodium carbonate slowly to pH = 7 and extract with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure to afford the title compound (10.6 g, 86percent). 'H-NMR (CDC13, 300 MHz) No. 9.10 (s, 1 H) ; 8.82 (s, 1 H).General procedure: 2-Hydroxy-3-nitropyridine 5 (0.015 mol) was suspended in POCla) Compound WXOO2-1 (295.68 mg, 662.13 tmol) and compound WXOO1-2 (354.9 mg, 1.30 nmol) weredissolved in acetonitrile (3.00 mE) at room temperature, followed by the addition of potassium carbonate (183.03mg, 1.32 mmol). The reaction mixture was heated at roomtemperature and stirred for 2 hours. After the reaction, themixture was diluted with water (10 mE) and extracted withethyl acetate (5 mEx2). The organic phases were combinedand dried over anhydrous sodium sulfate, followed byfiltration. The filtrate was concentrated under reduced pressure to remove the solvent. The obtained residue wasisolated by column chromatography (eluent: petroleumether/ethyl acetate=1 0/1-2/1, volume ratio) to obtain thetarget product WXOO2-2. MS-ESI mlz: 464.0 [M+H].Production Method of 2-Methyl-1-phenylpropan-2-yl 3-(3-ethylthio-5-trifluoromethylpyridin-2-yl)-2-(3-nitro-5-trifluoromethylpyridin-2-yl)-3-oxo-propionate Sodium hydride (240 mg, 3 Eq) was dissolved in DMA (dimethylacetamide) (2 mL). Under ice cooling, a DMA solution (2 mL) of 2-methyl-1-phenylpropan-2-yl 3-(3-ethylthio-5-trifluoromethylpyridin-2-yl)-3-oxo-propionate (895 mg, 2 mmol) was slowly added to the solution, and the mixture was stirred for 30 minutes. After that, a DMA solution (2 mL) of Reference Production Method of 2-methyl-1-phenylpropan-2-yl 3-(3-ethylthio-5-trifluoromethylpyridin-2-yl)-2-(3-nitro-5-trifluoromethylpyridin-2-yl)-3-oxo-propionate Sodium hydride (240 mg, 3 Eq) was dissolved in dimethylacetamide (DMA) (2 mL). To this, a DMA solution (2 mL) of 2-methyl-1-phenylpropan-2-yl 3-(3-ethylthio-5-trifluoromethylpyridin-2-yl)-3-oxo-propionate (895 mg, 2 mmol) was slowly added under ice cooling, and the mixture was stirred for 30 minutes. Then, a DMA solution (2 mL) of

Molecular Weight:226.54
XLogP3:2.5
Hydrogen Bond Acceptor Count:6
Exact Mass:225.9756895
Monoisotopic Mass:225.9756895
Topological Polar Surface Area:58.7
Heavy Atom Count:14
Complexity:230
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes