METHYL 4-AMINO-2-FLUOROBENZOATE

Step 2: Methyl 2-fluoro-4-nitrobenzoate (1 .05 g, 5.273 mmol) was dissolved in MeOH. Pd/C (105 mg) was added to the resulting mixture. The reaction mixture was stirred at room temperature for 2 hours under H2. The mixture was filtered through Celite and the filtrate was concentrated under reduced pressure. The crude was purified by column chromatography to give pure compound methyl 4-amino-2-fluorobenzoate (870 mg, 98 percent).Reflux the mixture of 2-fluoro-4-nitro-benzoic acid methyl ester [(0.] 85 g), ammonium formate (1.1 g) and [PD/C] (10percent, 0.32 g) in ethanol (20 mL) at [95C] for 6 hours. Filter over [CELITE0] and concentrate under reduced pressure to provide (0.64 g, 89percent) a gray solid.Step 1. Compound 12a (24 g, 154.71 mmol) was dissolved in methanol (300 mL) at 25° C., then thionyl chloride (27.61 g, 232.07 mmol) was added at 0° C. and reacted at 50° C. for 16 hours under nitrogen protection. After the reaction was completed, it was concentrated, diluted with water (300 mL) and extracted with ethyl acetate (100×3). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to give compound 12b (23.8 g).Example 7Synthesis of 2-cyano-3-(2-fluoro-4-(7-pivaloyl-5H-pyrrolo[2, 3-b]pyrazin-2-ylamino)phenyl)-dimethylacrylamideStep 1To a 250 ml three necked round bottom flask, Under a nitrogen atmosphere, a compound I (20.0 g, 0.060 mol) and a compound II (X=OCH3) (12.1 g, 0.072 mol) were added to a 500 mL three-necked flask at room temperature.Potassium carbonate (24.8 g, 0.180 mol) and acetonitrile (200 mL), mechanically stirred, And warming up to reflux, After 8 h of reaction, the reaction was stopped, the temperature was lowered to room temperature, and concentrated to 50 mL.Add 200mL of water and filter it to dry it like a white solid.20.4g, The yield was 80.6%.Add 2-fluoro-4-aminobenzoic acid methyl ester 2 (3.70 g, 21.8 mmol), cyclobutanone (2.44 g, 34.8 mmol), potassium cyanide (2.12 g, 32.6 mmol) and 37 mL to a 250 mL two-necked flask. Acetic acid, the temperature was raised to 80 C for 12 h, TLC monitoring reaction, (petroleum ether: ethyl acetate = 20:3), after the reaction was completed, 20 mL of water was added to the reaction solution, ethyl acetate extraction (30 × 3 mL), decompression In addition to the solvent, Compound 3, 5.01 g, brown red solid, yield: 92.5%.Add in a 150 mL two-necked flask at room temperature 2-fluoro-4-aminobenzoic acid ester 2 (4.5 g, 26.6 mmol), acetone (2.99 g, 42.7 mmol), potassium cyanide (2.6 g, 40 mmol) and 46 mL of acetic acid, the mixture was heated to 75 C for 24 h, and the reaction was monitored by TLC ( petroleum ether: ethyl acetate = 20:3). After the reaction was completed, 20 mL of water was added to the reaction mixture, and ethyl acetate (40×3 mL) was evaporated.The residue was dissolved by adding a mixed solvent of 6 mL of ethanol and 5 mL of water. cooling crystals, filtering to give compound 21, 3.13 g, yellow solid, yield 50.2%.

Molecular Weight:169.15
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:169.05390666
Monoisotopic Mass:169.05390666
Topological Polar Surface Area:52.3
Heavy Atom Count:12
Complexity:174
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes