4-Trifluoromethylnicotinamide

(Reference Example 8) (Reference Example 12) (Reference Example 11) (Reference Example 9) (Reference Example 10) In a 250 mL reactor equipped with a reflux condenser was added 19 g (0.1 mol) Of 4- (trifluoromethyl) nicotinamide, 17.9 g (0.12 mol) of N, N-diethylaniline and 80 g of toluene, 8.25 g (0.1 lmo 1) of chloroacetonitrile was added dropwise at a temperature of 15 ± 5 C, The reaction temperature was then raised to 60 C for 6 h. After the completion of the reaction, the liquid layer was analyzed by liquid chromatography, and as a result, the yield (selectivity) of N-cyanomethyl-4- (trifluoromethyl) nicotinamide was 98.2%, 4- (trifluoromethyl ) Nicotinamide was 98.7%, and the yield was selective, and the yield was obtained in the absence of separation and purification.After oxalyl chloride (0. 14ml) was added to a suspension of Sodium hydride (0.090g, 60% dispersion in mineral oil) was added to a solution of 4- trifluoromethyl-3-pyridinecarboxamide (0.40g) in N, N-dimethylformamide at 20C, and stirred for 1 hour. Benzyl isocyanate (0.31 mi) was added and the mixture stirred at 20C for 2 hours, then methyl bromoacetate (0.30 ml) added and stirring continued for 5 hours. Ethyl acetate and water were added to the solution and the organic phase dried (magnesium sulfate), evaporated and the residue purified by column chromatography on silica gel, eluting with n-hexane/ethyl acetate (2: 1), to give 3-benzyl-1- (4-trifluoromethyl-3-pyridylcarbonyl) hydantoin (0.50g, Compound S- 132).SYNTHESIS EXAMPLE 3 Preparation of 4-trifluoromethyl-3-pyridine carboxamide (Compound No. 5) A solution comprising 3 g of 4-trifluoromethyl-3-pyridine carboxylic acid, 6.7 ml of thionyl chloride and 20 ml of benzene, was refluxed under heating for 1.5 hours in the presence of a catalytic amount of dimethylformamide. Excess thionyl chloride and benzene were distilled off. Then, the residue was dissolved in 5 ml of ethyl acetate. This solution was gradually dropwise added to 20 ml of ammonia under cooling with ice. After completion Of the dropwise addition, the mixture was stirred at room temperature for 30 minutes. Then, water and ethyl acetate were distilled off under reduced pressure. The residue was extracted with heated ethyl acetate to obtain 2.1 g of 4-trifluoromethyl-3-pyridine carboxamide (melting point: 162.7 C.) as the desired product.(2) 9.2 g of 2, 6-dichloro-4-trifluoromethyl-3-pyridine carboxamide obtained in the above step (1), 0.66 g of 10% palladium carbon and 6.4 g of anhydrous sodium acetate were added to 200 ml of methanol. Then, a reduction reaction was conducted under a hydrogen pressure at room temperature for 12 hours. After completion of the reaction, the reducing catalyst was removed by Celite, and the filtrate was concentrated. Extraction was conducted by adding ethyl acetate and water to the residue. The organic layer was dried over anhydrous sodium sulfate. Then, the solvent was distilled off to obtain 5.2 g of 4-trifluoromethyl-3-pyridine carboxamide as the desired product.Weigh 12.95 g of 2, 6-dichloro-four, Add 2, 6-dichloro-SYNTHESIS EXAMPLE 10 Preparation of 4-trifluoromethyl-3-pyridine carboxamide 1-oxide (Compound No. 11) 0.8 g of 4-trifluoromethyl-3-pyridine carboxamide was dissolved in 7 ml of acetic acid. Then, 0.72 g of a 30% hydrogen peroxide aqueous solution was gradually dropwise added thereto. After completion of the dropwise addition, the reaction solution was heated to 70 C. and stirred for 8 hours at this temperature. After completion of the reaction, the solvent was distilled off under reduced pressure. The residue thereby obtained was washed with n-hexane to obtain 0.6 g of 4-trifluoromethyl-3-pyridine carboxamide 1-oxide (melting point: 198.8 C.) as the desired product.Oxalyl chloride (0. 1 5moi) was added to a suspension of 4-trifluoromethyl-3- pyridinecarboxamide (0.25g) in 1, 2-dichloroethane at 20C and then heated to reflux for 2 hours. The mixture was cooled, evaporated and the residue containing 4- trifluoromethyl-3-pyridylcarbonyl isocyanate was dissolved in tetrahydrofuran.; Oxalyl chloride (1. 50ml) was added to a suspension of 4-trifluoromethyl-3- pyridinecarboxamide (2. 0g) in 1, 2-dichloroethane at 20C, and stirred under reflux for 2 hours. The mixture was evaporated and dichloromethane added to the residue containing 4-trifluoromethyl-3-pyridylcarbonyl isocyanate.

Molecular Weight:190.12
XLogP3:0.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:1
Exact Mass:190.03539727
Monoisotopic Mass:190.03539727
Topological Polar Surface Area:56
Heavy Atom Count:13
Complexity:204
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes