Application of a kind of ethylbenzamide compound in preparation of local anesthetic
A technology of ethylbenzamide and local anesthetics, which is applied in the field of application of ethylbenzamide compounds in the preparation of local anesthetics, and can solve the problems that local anesthetics have not yet been developed
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[0047] The preparation method of compound A1-21
[0048] React substituted benzoyl chloride with 2-bromoethylamine to obtain intermediate A; react piperazine with benzoyl chloride to obtain intermediate C; react intermediate A with intermediate C to obtain the target compound; the reaction formula is as follows:
[0049]
[0050] Synthesis of Intermediate A: Put 0.1mol 2-bromoethylamine in a round-bottomed flask, add 0.2mol triethylamine, then slowly add 0.1mol substituted benzoyl chloride dropwise in an ice bath, react at room temperature overnight, and white crystals precipitate out. Suction filtration, drying, toluene recrystallization, that is.
[0051] Synthesis of intermediate C: phenylalkanoic acid and thionyl chloride were heated under reflux in a round-bottomed flask for 5 hours, excess thionyl chloride was evaporated, and distillation under reduced pressure was carried out to obtain phenylalkanoyl chloride; piperazine hexahydrate and Stir the glacial acetic acid ...
Embodiment 1
[0055] Synthesis of Compound A1: Intermediate A was synthesized using 3-fluorobenzoyl chloride, and Intermediate C was synthesized using phenylacetyl chloride. The yield was 83%, and mp: 176-178°C.
[0056] 1H NMR (300 MHz, CDCl 3 ), δ: 8.84 (s, 1H, -NH-), 7.81 (m, 2H, Ph-H), 6.98 (m, 2H, Ph-H), 3.60 (m, 2H, -CH 2 -), 2.65(m, 4H, -CH 2 -), 2.50(m, 2H, -CH 2 -), 4.54(m, 6H, -CH 2 -), 8.02(m, 3H, Ph-H), 6.73 (m, 2H, Ph-H), 1.07(s, 1H, -NH-); HR-ESI-MS m / z: calcd forC 21 h 24 N 3 o 2 F{[M+H] +} 369.2.
Embodiment 2
[0058] Synthesis of Compound A5: Intermediate A was synthesized using 2-methoxybenzoyl chloride, and Intermediate C was synthesized using phenylacetyl chloride. The yield was 82%, and mp: 167-168°C.
[0059] 1H NMR (300 MHz, CDCl 3 ), δ: 8.84 (s, 1H, -NH-), 7.81 (m, 2H, Ph-H), 6.98 (m, 2H, Ph-H), 3.60 (m, 2H, -CH2 -), 2.65(m, 4H, -CH 2 -), 2.50(m, 2H, -CH 2 -), 4.54(m, 6H, -CH 2 -), 3.81(s, 3H, -CH 3 ), 8.02(m, 3H, Ph-H), 6.73 (m, 2H, Ph-H), 1.07(s, 1H, -NH-); HR-ESI-MS m / z: calcd for C 22 h 27 N 3 o 3 {[M+H] +} 381.3.
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