* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
b Preparation of ethyl 3-phenylsulfanyl-2-(S)-[(2-pyridin-4-yl-1H-benzimidazole-5-carbonyl)amino]propionate: In this case, the standard TOTU coupling with 188 mg (0.83 mmol) of ethyl 2-(S)-amino-3-phenylsulfanylpropionate and 200 mg (0.83 mmol) of 2-pyridin-4-yl-1H-benzimidazole-5-carboxylic acid yielded the desired product. Yield: 43% (160 mg, 0.36 mmol).
2
5-(1-amino-3-phenylpropyl)-[1,3,4]oxadiazol-2-ylamine[ No CAS ]
[ 316833-32-6 ]
[ 1634-04-4 ]
2-pyridin4-yl-1H-benzimidazole-5-carboxylic acid [1-(5-amino-[1,3,4]oxadiazol-2-yl)-3-phenylpropyl]amide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With diisopropylamine; In N-methyl-acetamide; ethyl acetate;
d Preparation of 2-pyridin4-yl-1H-benzimidazole-5-carboxylic acid [1-(5-amino-[1,3,4]oxadiazol-2-yl)-3-phenylpropyl]amide: 0.18 g of 5-(1-amino-3-phenylpropyl)-[1,3,4]oxadiazol-2-ylamine was dissolved in 10 ml of dry dimethylformamide at RT, treated with 200 mg of <strong>[316833-32-6]2-pyridin-4-yl-1H-benzimidazole-5-carboxylic acid</strong>, 270 mg of TOTU, and 0.12 ml of diisopropylamine, and stirred at RT for 4 h. The reaction mixture was concentrated, and the residue was taken up in ethyl acetate and washed successively with water, saturated sodium hydrogencarbonate solution, water, and saturated sodium chloride solution. The organic phase was dried over magnesium sulfate, filtered, and concentrated. The residue was stirred with methyl tert-butyl ether, filtered off, and dried under high vacuum. 2-Pyridin4-yl-1H-benzimidazole-5-carboxylic acid [1-(5-amino-[1,3,4]oxadiazol-2-yl)-3-phenylpropyl]amide, which melts at 160 C. with decomposition, is obtained.
2-pyridin-4-yl-1H-benzimidazole-5-carboxylic acid {1-[5-(3-methylureido)-[1,3,4]oxadiazol-2-yl]-3-phenylpropyl}amide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With diisopropylamine; In ethyl acetate; N,N-dimethyl-formamide;
e Preparation of <strong>[316833-32-6]2-pyridin-4-yl-1H-benzimidazole-5-carboxylic acid</strong> {1-[5-(3-methylureido)-[1,3,4]oxadiazol-2-yl]-3-phenylpropyl}amide: 40 mg of the previous compound was dissolved in 3 ml of dry DMF at RT and treated successively with 33 mg of <strong>[316833-32-6]2-pyridin-4-yl-1H-benzimidazole-5-carboxylic acid</strong>, 20 mul of diisopropylamine, and 40 mg of TOTU and stirred at RT for 4 h. The reaction mixture was concentrated in vacuo; the residue was taken up in ethyl acetate/tetrahydrofuran (1/1), washed with water, saturated sodium hydrogencarbonate solution, and saturated sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. 2-Pyridin-4-yl-1H-benzimidazole-5-carboxylic acid {1-[5-(3-methylureido)-[1,3,4]oxadiazol-2-yl]-3-phenylpropyl}amide was obtained, which has m/e=497.3 (=MH+) in the mass spectrum.
1-[1,3,4]oxadiazol-2-yl-3-phenylpropylamine[ No CAS ]
[ 316833-32-6 ]
2-pyridin-4-yl-1H-benzimidazole-5-carboxylic acid (1-[1,3,4]oxadiazol-2-yl-3-phenylpropyl)amide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With diisopropylamine; In N-methyl-acetamide; methanol; dichloromethane; ethyl acetate;
d Preparation of <strong>[316833-32-6]2-pyridin-4-yl-1H-benzimidazole-5-carboxylic acid</strong> (1-[1,3,4]oxadiazol-2-yl-3-phenylpropyl)amide: 220 mg of 1-[1,3,4]oxadiazole-2-yl-3-phenylpropylamine were dissolved in 10 ml of dry dimethylformamide at RT, treated with 260 mg of 2-pyridin-4-yl-1H-benzimidazol-5-carboxylic acid, 350 mg of TOTU, and 0.15 ml of diisopropylamine, and stirred at RT for 4 h. The reaction mixture was concentrated, the residue was taken up in ethyl acetate, and the mixture was washed successively with water, saturated sodium hydrogencarbonate solution, water, and saturated sodium chloride solution. The organic phase was dried over magnesium sulfate, filtered, and concentrated. The residue was chromatographed on silica gel using dichloromethane/methanol (8/1) and yielded <strong>[316833-32-6]2-pyridin-4-yl-1H-benzimidazole-5-carboxylic acid</strong> (1-[1,3,4]oxadiazol-2-yl-3-phenylpropyl)amide, which melts at 103 C. with decomposition.
2-pyridin-4-yl-1H-benzimidazole-5-carboxylic acid [3-phenyl-1-(1H-tetrazol-5-yl)propyl]amide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With diisopropylamine; In methanol; dichloromethane; water; acetic acid; ethyl acetate; N,N-dimethyl-formamide;
d Preparation of <strong>[316833-32-6]2-pyridin-4-yl-1H-benzimidazole-5-carboxylic acid</strong> [3-phenyl-1-(1H-tetrazol-5-yl)propyl]amide: 0.9 mmol of the compound of Example 194c was dissolved in 5 ml of dry DMF and treated with 0.9 mmol of <strong>[316833-32-6]2-pyridin-4-yl-1H-benzimidazole-5-carboxylic acid</strong>, 0.365 ml of diisopropylamine, and 415 mg of TOTU, and stirred at RT for 20 h and at 50 C. for a further 4 h. The reaction mixture was concentrated in vacuo; the residue was taken up in ethyl acetate, washed with water, saturated sodium hydrogencarbonate solution, and saturated sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude product thus obtained was chromatographed on silica gel using dichloromethane/methanol/water/glacial acetic acid (60/10/1/1). 2-Pyridin-4-yl-1H-benzimidazole-5-carboxylic acid [3-phenyl-1-(1H-tetrazol-5-yl)propyl]amide, was obtained, which decomposed at 87 C. and had a molecular peak at m/e=425.2 (=MH+), is obtained.
L-4-([1,3,4]oxadiazol-2-yl)-2-aminobutanoic acid morpholide[ No CAS ]
2-pyridin-4-yl-1H-benzimidazole-5-carboxylic acid [1-(morpholine-4-carbonyl)-3-[1,3,4]oxadiazol-2-ylpropyl]amide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In water; N,N-dimethyl-formamide; acetonitrile;
d Preparation of <strong>[316833-32-6]2-pyridin-4-yl-1H-benzimidazole-5-carboxylic acid</strong> [1-(morpholine-4-carbonyl)-3-[1,3,4]oxadiazol-2-ylpropyl]amide: 43 mg of <strong>[316833-32-6]2-pyridin-4-yl-1H-benzimidazole-5-carboxylic acid</strong>, 75 mg of HATU, and 51 mg of diisopropylethylamine were dissolved in 1 ml of N,N-dimethylformamide and treated with 40 mg of L-4-([1,3,4]oxadiazol-2-yl)-2-aminobutanoic acid morpholide in 0.4 ml of N,N-dimethylformamide after stirring for 10 min. After stirring at RT for 7 h, 200 mg of aminomethylpolystyrene (1.37 mmol/g) and 20 ml of N,N-dimethylformamide were added. After 1 h, the mixture was filtered and the N,N-dimethylformamide was distilled off under reduced pressure. The residue was digested with cold acetonitrile. The insoluble residue was discarded and the acetonitrile solution was subjected to gradient filtration on RP18 silica gel using water/acetonitrile mixtures. A glassy yellowish solid was isolated.
General procedure: A mixture of appropriate 2-substituent-1H-benzimidazole-4/5-carboxylic acid (1 mmol), EDC·HCl (0.37 g, 2.0 mmol) and HOBt (0.27 g, 2.0 mmol) in DMF or DCM (10 mL) was stirred for 1 h at room temperature. Then N-hydroxyacetamidine (1.05 mmol) was added and stirred for 24 h. 20 mL water was added and the precipitate was filtered, dried. The products were purified on silica gel column.
General procedure: Appropriate aldehyde 3 (1.5 mmol) was added to the solution of 2,3/3,4-diaminobenzoic acid 2 (1.0 mmol) in dioxane (10 mL). 1,4-Benzoquinone was added and the solution was heated to 80 C and stirred for about 6-9 h.Then, the solution was cooled to room temperature. The separated solid crystals were filtered, washed with ethanol and ether, dried. The products were used in the next step without further purification.
2-(4-(trifluoromethyl)phenyl)-2,8-diazaspiro[4.5]decan-3-one[ No CAS ]
8-(2-(pyridin-4-yl)-1H-benzo[d]imidazole-5-carbonyl)-2-(4-(trifluoromethyl)phenyl)-2,8-diazaspiro[4.5]decan-3-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 40℃; for 20h;
General procedure: A mixture of intermediates 4a-e (0.60 mmol), EDCI (138 mg,0.72 mmol), corresponding carboxylic acid derivatives (0.60 mmol)and HOBt (97 mg, 0.72 mmol) in N,N-dimethylformamide (6.0 mL)was stirred for 20 h. The reaction mixture was diluted with ethylacetate and washed with brine, the organic layer was dried over magnesium sulfate and concentration in vacuo. The residue waspurified by silica gel column chromatography (5% methanol/chloroform)to afford the title compounds 6a-t as a white solid.
With tetrafluoroboric acid; 1,10-Phenanthroline; In dimethyl sulfoxide; N,N-dimethyl-formamide; at 100℃; for 168h;
0.6 mmol of <strong>[316833-32-6]2-(4-pyridyl)benzimidazole-5-carboxylic acid</strong>, 0.3 mmol of cadmium nitrate and 0.6 mmol of 1,10'-phenanthroline were sequentially added to a small glass bottle, and then 15 ml of N,N-dimethylformamide and 3 ml of dimethyl sulfoxide were sequentially added to the above small glass bottle, and stirred at room temperature. During the stirring, tetrafluoroboric acid was appropriately added until the solution became clear, and it was allowed to stand at 100 C. The reaction in the incubator takes about one week until the colorless bulk crystal material is found, cooled to room temperature, filtered and dried, and then the synthesized nitrogen-containing carboxylic acid transition metal cadmium pore complex material is obtained.The calculated yield was 60%.
With tetrafluoroboric acid; 1,10-Phenanthroline; In dimethyl sulfoxide; N,N-dimethyl-formamide; at 80℃; for 168h;
0.4 mmol of <strong>[316833-32-6]2-(4-pyridyl)benzimidazole-5-carboxylic acid</strong>, 0.2 mmol of cadmium acetate and 0.4 mmol of 1,10'-phenanthroline were sequentially added to a small glass bottle, and then 10 ml of N,N-dimethylformamide and 2 ml of dimethyl sulfoxide were sequentially added to the above small glass bottle, and stirred at room temperature. During the stirring, tetrafluoroboric acid was appropriately added until the solution became clear, and the solution was allowed to stand at 80 C. The reaction in the incubator takes about one week until the colorless bulk crystal material is found, cooled to room temperature, filtered and dried, and then the synthesized nitrogen-containing carboxylic acid transition metal cadmium pore complex material is obtained.The calculated yield was 60%.
With tetrafluoroboric acid; 1,10-Phenanthroline; In dimethyl sulfoxide; N,N-dimethyl-formamide; at 100℃; for 168h;
0.6 mmol of <strong>[316833-32-6]2-(4-pyridyl)benzimidazole-5-carboxylic acid</strong>, 0.3 mmol of cadmium zinc nitrate and 0.6 mmol of 1,10'-phenanthroline were sequentially added to a small glass bottle, and then 15 ml. N, N-dimethylformamide, 3 ml of dimethyl sulfoxide were sequentially added to the above small glass bottle, stirred at room temperature, and tetrafluoroboric acid was appropriately added to the solution during the stirring to become a clarified state, and allowed to stand at 100. The reaction is carried out in a C incubator for a week or so until the colorless bulk crystal material is found, cooled to room temperature, filtered and dried., obtaining a synthetic nitrogen-containing carboxylic acid transition metal cadmium pore complex material,The calculated yield was 62%.