|
With phosphorus pentachloride at 50 - 60℃; |
|
|
With thionyl chloride |
|
|
With thionyl chloride In dichloromethane for 8h; Heating; |
|
|
With pyridine; thionyl chloride In toluene at 80℃; for 3h; |
|
|
With thionyl chloride In dichloromethane Heating; |
|
|
With thionyl chloride In dichloromethane; N,N-dimethyl-formamide; toluene |
B.1 EXAMPLE B-1
EXAMPLE B-1 In 5 ml of methylene chloride was suspended 0.25 g of 4-isopropylbenzoic acid. Then, at ambient temperature, 0.12 ml of thionyl chloride and 0.03 ml of N,N-dimethylformamide were added. After stirring the mixture at the same temperature as above for one hour, the solvent was distilled off under reduced pressure, and an azeotropic distillation treatment using toluene was carried out to obtain 0.25 g of 4-isopropylbenzoic acid chloride. |
|
With pyridine; thionyl chloride In toluene |
55.B B.
B. 2-(4-Isopropylbenzoylamino)-N-(4-methoxyphenyl)benzamide To a mixture of 4-isopropylbenzoic acid (191 mg, 1.16 mmol) and pyridine (0.12 mL, 1.5 mmol) in toluene (10 mL) was added thionyl chloride (0.11 mL, 1.5 mmol). After heating at 80° C. for 3 h, the reaction mixture was cooled and concentrated in vacuo to give 4-isopropylbenzoyl chloride. |
|
With chloroformic acid ethyl ester; triethylamine In dichloromethane at 0℃; for 0.5h; |
|
|
With thionyl chloride In toluene for 1h; Heating / reflux; |
89
Intermediate 89; Methyl 3-r4-(ir4-(1-methylethyl)phenyllcarbonyl}amino)butyll-1 -(2-pyridinyl)-1H- indole-5-carboxylate; To a solution of 4-(1-methylethyl)benzoic acid (76 mg, 0.46 mmol) in toluene (5 ml) was added thionyl chloride. The mixture was stirred at reflux for 1 hour. Then, thionyl chloride was eliminated by co-evaporation with toluene to give 4-(1 -methylethyl)benzoyl chloride, methyl 3-(4-aminobutyl)-1 -(2-pyridinyl)-1 H-indole-5-carboxylate (Intermediate 88) (100 PB62659Cmg, 0.31 mmol) was dissolved in anhydrous THF (10 ml), triethylamine (62 μl, 0.46 mmol) was added and 4-(1-methylethyl)benzoyl chloride was poured into the mixture. The reaction is stirred at room temperature for 2 days. The mixture was hydrolysed with water and extracted with ethyl acetate. The organic phase was washed with water and dried over Na2SO4, filtered and evaporated to dryness. The residue was purified on SiO2 eluting with dichloromethane to give the title compound as brown oil (1 10 mg, 76%). LC/MS : m/z 470 (M+H)+, Rt: 3.68. |
|
With oxalyl dichloride |
|
|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 4h; |
4.1.1. General method A. N-(3-Bromo-2-methylphenyl)-4-(tertbutyl)benzamide (S1a)
General procedure: To a mixture of 4-(tert-butyl)benzoic acid (1 g, 5.61 mmol) in DCM (30 mL) was added oxalyl chloride (0.57 mL, 6.74 mmol) and DMF (0.05 mL) at 0 °C. The reaction mixture was stirred at room temperature for 4 h. The resulting mixture was then concentrated to afford the crude 4-(tert-butyl)benzoyl chloride. And then to a mixture of 3-bromo-2-methylaniline (1.11 g, 6 mmol) in dry DCM (50 mL) was slowly added crude 4-(tert-butyl)benzoyl chloride and DIPEA (1 mL, 5 mmol) at 0 °C. The resulting mixture was stirred for 10 min at room temperature, and then quenched by MeOH (5 mL), concentrated and purified by flash column chromatography (0-2%MeOH in DCM) to afford S1a (1.86 g, two steps yield 96%) as a white solid. |
|
With thionyl chloride at 80℃; for 2h; |
1
0.01 mol of p-isopropylbenzoic acid and 15 mL of thionyl chloride were added to a 50 mL three-necked flask, It was heated to 80 °C under reflux for 2 hours. The excess amount of thionyl chloride was removed by distillation under reduced pressure until the liquid was allowed to flow out and cooled to room temperature to give p-isopropylbenzoyl chloride. |
|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 3h; Inert atmosphere; |
|
|
at 80℃; for 2h; Alkaline conditions; |
Preparation of Acyl Chlorides (1a, 2a, and 3a).
General procedure: Thionyl chloride (15 mL) was added to 0.01 mol of the correspondingacids. The mixture was heated under reflux at 80C for 2 h with the help of a drying tube filled with anhydrous calciumchloride. The reaction was monitored by thin-layer chromatography (TLC). When the reaction was completed, excess thionylchloride was removed under reduced pressure. The crude products were used in the subsequent reaction without furtherpurification (Scheme 1). |
|
With thionyl chloride In toluene for 4h; Reflux; |
To a solution of 4-(1-methylethyl)benzoic acid (763 mg, 4.65 mM) in 30 ml of toluene was added 1.7 ml of thionyl chloride (23.25mM), the reaction mixture was stirred 4h under reflux. Toluene was evaporated under vacuum, 50 ml of toluene are added to the mixture and evaporated under vacuum. The crude oil was solubilized in 30 ml of CH2CI2, and that solution was added drop wise to solution of methyl 1-(4-aminobutyl)-3-phenyl-1 H-indole-6- carboxylate (Intermediate 21 ) (1g, 3.1 mM) in 100 ml of CH2CI2 + 622μl_ of triethylamine. The reaction mixture was stirred for VA hours at room temperature, washed with brine dried on Na2SO4, after evaporation the crude solid was purified on SiO2 to give methyl 1-[4-([4-(1-methylethyl)phenyl]carbonyl}amino)butyl]-3-phenyl-1 H-indole-6-carboxylate(1.1g, 76%).[APCI-MS] m/z: 469.12 (M+H)+, Rt= 3.87 min. |
|
With thionyl chloride; N,N-dimethyl-formamide for 6h; Reflux; |
|
|
With thionyl chloride Reflux; |
1.5 Synthesis of intermediate 6
General procedure: The corresponding acid compound 5 (10 mmol) was completely dissolved in 30 mL of SOCl2. The reaction was stirred at reflux temperature for 12 h. The mixture was evaporated under vacuum, the residue was dissolved in 10 mL of dry DCM and used in next step without purification. |
|
With oxalyl dichloride |
|
|
With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 3h; Inert atmosphere; |
4.2.2. General Procedure for the Synthesis of 4-Substituted Benzoyl Chlorides 4,5
General procedure: Oxalyl chloride (12 mmol) was added dropwise to a mixture of the appropriate 4-substituted benzoic acid2, 3(10 mmol), in anhydrous DCM (30 mL) and anhydrous DMF (10 µL) under nitrogen at 0 °C. The reaction mixture was stirred at room temperature for sn additional 3 h until the reaction was completed. The reaction mixture was evaporated under vacuum and the oily residue was used without further purification for the acid hydrazide preparation. |
|
With oxalyl dichloride In tetrahydrofuran at 0℃; for 2h; Inert atmosphere; |
General procedure for preparation of benzoyl chlorides 2a-w.
General procedure: To the solution of benzoic acids (2.4 mmol) in anhydrous THF(10 mL) under nitrogen atmosphere at 0 C was slowly added oxalylchloride (3.6 mmol). The reaction mixture was then stirred for 2-3 h under nitrogen. The reaction mixture was changed from transparent to a slightly yellowish color. The solvent was evaporatedon vacuo rotavapor, and the obtained product was directly used for the next reaction. |
|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; |
|
|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 3h; Cooling with ice; |
49 Example 49. Preparation of compound 49 with lappaconitine and 4-isopropyl benzoic acid:
Weigh 120mg of 4-isopropylbenzoic acid in a 25ml dry round bottom flask, add 10ml of dry dichloromethane to dissolve it, add a few drops of dimethylformamide, and add 129mg of oxalyl chloride in an ice bath. After reacting at room temperature for 3 hours, 4-isopropylbenzoyl chloride was prepared. Weigh 69 mg of N-deacetyllappaconitine in a 25 ml round-bottom flask, and add 10 ml of dry dichloromethane to dissolve it. Add 105μl of dry pyridine under the protection of Ar gas, slowly add the prepared acid chloride dropwise to the substrate solution, and react at 35°C. The progress of the reaction is checked by thin-layer chromatography. The reaction is complete after 17 hours. Add dropwise saturated sodium carbonate aqueous solution to the reaction solution, adjust the pH value of the reaction solution to 10, extract the reaction solution with dichloromethane, dry the dichloromethane layer with anhydrous sodium sulfate, filter off the sodium sulfate solid, and spin-dry the dichloromethane to obtain The crude product is separated and purified by column chromatography to obtain the target compound. Its structure and characteristics are as follows: |
|
With oxalyl dichloride In dichloromethane at 0 - 30℃; |
|
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
