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CAS No. : | 1612-76-6 | MDL No. : | MFCD00126383 |
Formula : | C8H7N3O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | CQSFYCBGVMWPCM-UHFFFAOYSA-N |
M.W : | 161.16 | Pubchem ID : | 15363 |
Synonyms : |
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 11 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 44.14 |
TPSA : | 64.94 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.13 cm/s |
Log Po/w (iLOGP) : | 1.53 |
Log Po/w (XLOGP3) : | 1.63 |
Log Po/w (WLOGP) : | 1.33 |
Log Po/w (MLOGP) : | 1.17 |
Log Po/w (SILICOS-IT) : | 1.22 |
Consensus Log Po/w : | 1.38 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.48 |
Solubility : | 0.536 mg/ml ; 0.00332 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.61 |
Solubility : | 0.399 mg/ml ; 0.00248 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.01 |
Solubility : | 0.156 mg/ml ; 0.000971 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.28 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With triethylamine; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In dichloromethane at 0℃; for 0.166667h; | |
80% | With Oxone; iodine; sodium hydroxide In water; isopropyl alcohol at 0 - 20℃; for 0.5h; | |
70% | With N-ethyl-N,N-diisopropylamine; diisopropyl-carbodiimide In acetonitrile at 40 - 50℃; for 24h; |
62% | With sodium hydroxide; 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; potassium iodide In water; isopropyl alcohol; acetonitrile at 5℃; | |
45% | With sodium hydroxide; dimethyl sulfate at 60℃; | |
41% | Stage #1: benzoyl thiosemicarbazide With potassium iodide; sodium hydroxide In water at 0℃; for 0.0833333h; Stage #2: With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione In water at 0 - 25℃; for 7h; | 5-(5-Chlorothiophen-2-yl)-1,3,4-oxadiazol-2-amine (2A). General procedure: To a cold (0 oC) solution of 0.61 g (3.69mmol) of KI in 7 mL of water were added 2.9 g (12.3 mmol) of 18A, 20 mL of water, and 4.6 mL of 4 N NaOH solution (18.5 mmol) and the resulting solution was stirred for 5 min. To it, was added 3.87 g (13.5 mmol) of 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) and the solution was stirred at 25 oC for 7h, diluted with 3.6 mL of saturated NaHSO3 aqueous solution, and extracted four times with EtOAc (150mL each). The combined organic layers were washed with brine, dried (anhydrous Na2SO4),concentrated, and crystallized from EtOAc (80 mL) to yield 1.20 g (49% yield) of compound 2A as white solids, mp 250 - 253 oC. 1H NMR (DMSO-d6): δ 7.33 - 7.38 (m, 3H), 7.24 (d, J = 4.3 Hz, 1H) ppm. 13C NMR (DMSO-d6): δ 163.5, 152.6, 130.7, 128.3, 126.9, 124.6 ppm. MS (positive mode): m/z calcdfor C6H5ClN3OS (M+H)+: 202.0, found 202.0. |
With ethanol; lead(II) oxide | ||
With ethanol; lead(II) oxide | ||
With mercury(II) oxide In ethanol for 6h; Heating; | ||
Multi-step reaction with 2 steps 1: aq. NaOH solution / anschliessend Behandeln mit einer Loesung von Methyljodid in Aethanol | ||
Multi-step reaction with 2 steps 1: aq. NaOH solution / anschliessend Behandeln mit einer Loesung von Methyljodid in Aethanol 2: 200 °C | ||
Multi-step reaction with 2 steps 1: aq. NaOH solution / anschliessend Behandeln mit einer Loesung von Methyljodid in Aethanol 2: ethanolic sodium ethylate | ||
With water; iodine; potassium iodide; sodium hydroxide In ethanol at 70℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Ambient temperature; | |
94% | Stage #1: bromocyane With 1,2,3-Benzotriazole Stage #2: benzoic acid hydrazide In tetrahydrofuran for 3h; Heating; | |
62% | In methanol for 4h; Reflux; | 4 2-Amino-5-phenyl-1,3,4-oxadiazole (2) 15 g (110 mmol) of 1 and 13 g (122 mmol) cyanogens bromide were dissolved in methanol (100 ml) and were refluxed for 4 h. The solvent was evaporated and the residue recrystallized from isopropyl alcohol and water to give 11 g (62%) of 2. Mp: 246-248 °C; IR: (KBr) ν (cm-1) 3305, 3123, 1663, 1651; mass m/z (%): 161 (M+, 100), 118 (98), 105 (74), 103 (70), 91 (61), 77 (87). Anal. Calcd for C8H7N3O: C, 59.62; H, 4.38; N, 26.07. Found: C, 59.85; H, 4.40; N, 25.87. |
With potassium hydrogencarbonate | ||
With methanol | ||
With potassium hydrogencarbonate In water; acetonitrile |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With carbon tetrabromide; Eosin In acetonitrile at 20℃; Irradiation; | General Procedure for the Synthesis of 5-Aryl-1,3,4-Oxadiazoles2 General procedure: A solution of semicarbazone 1 (1 mmol), CBr4 (1 mmol), andeosin Y (3, 1 mol%) in MeCN (3 mL) was irradiated with greenLED at r.t. in an air atmosphere for 10-14 h. After completion ofthe reaction (indicated by TLC), it was quenched with sat. aqNaHCO3 (5 mL) and extracted with EtOAc (3 × 5 mL). The combinedorganic phases were dried over anhydrous Na2SO4, filtered,and the solvent was removed under reduced pressure.The resulting crude product was purified by flash chromatographyon silica gel [200-300 mesh; eluent: hexane-EtOAc (10:1 to5:1)] to afford an analytically pure sample of 2-amino-5-aryl-1,3,4-oxadiazole 2. All the compounds are known and werecharacterized by comparison of their spectroscopic data withthose reported in the literature (see ref. 45). |
85% | With bromine; anhydrous Sodium acetate In acetic acid for 0.25h; | |
85% | With bromine; anhydrous Sodium acetate; acetic acid | General procedure for 5-substituted-aryl-1,3,4-oxadiazol-2-amines (4a-l) General procedure: A mixture of synthesized compound 2-benzylidenehydrazine-1-carboxamide (1.63 g, 0.01 mole) (3a) and sodium acetate(1.64 g, 0.02 mole) were stirred continuously in 30-40ml ofglacial acetic acid. In the reaction mixture bromine, (1.4ml in10 ml of GAA) was added dropwise and stirred for another1-4 h. After completion, it was poured on ice and the solidgets separated. The solid was filtered and leftover for drying.Finally, it was recrystallized from ethanol to get 5-phenyl-1,3,4-oxadiazol-2-amine (4a) in a yield of 85% [10]. Theother derivatives 4b-l were similarly synthesized by theabove methods. |
85% | With bromine; anhydrous Sodium acetate; acetic acid | General procedure for 5-substituted-aryl-1,3,4-oxadiazol-2-amines (4a-l) General procedure: A mixture of synthesized compound 2-benzylidenehydrazine-1-carboxamide (1.63 g, 0.01 mole) (3a) and sodium acetate(1.64 g, 0.02 mole) were stirred continuously in 30-40ml ofglacial acetic acid. In the reaction mixture bromine, (1.4ml in10 ml of GAA) was added dropwise and stirred for another1-4 h. After completion, it was poured on ice and the solidgets separated. The solid was filtered and leftover for drying.Finally, it was recrystallized from ethanol to get 5-phenyl-1,3,4-oxadiazol-2-amine (4a) in a yield of 85% [10]. Theother derivatives 4b-l were similarly synthesized by theabove methods. |
82% | With bromine; anhydrous Sodium acetate; acetic acid at 20℃; for 7h; | 1.2 Steps 2 the8.16g (0.05mol) of benzaldehyde semicarbazone and 8 20g(0 .1mol) Anhydroussodium acetate placed in a flask, added 80ml of Glacial acetic acid to dissolve,after dissolving added 2.56ml(0.05mol) Bromine, the addition was complete,atroom temperature keep the reaction for 7h, completion of the reaction, thenadded crushed ice, white solid precipitated, suction filtration , dried , recrystallizedfrom ethanol to obtain 6.58g of white solid 2-amino-5-phenyl-1,3,4-oxadiazole, Yield:82%, |
82% | With bromine; anhydrous Sodium acetate; acetic acid at 20℃; for 5h; | 1.2 Step 2 8 · 16g (0 · 05mol) benzaldehyde semicarbazone and 8 · 20g (0 · lmol) of anhydrous sodium acetate into a flask, 55mL glacial acetic acid to dissolve, adding .56mL dissolved (0.05 mol) bromine addition was complete, the reaction 5H room temperature, the reaction is completed, crushed ice was added, the white solid was precipitated, suction filtration, dried, and recrystallized from ethanol to give 6.58g of white solid 2-amino-5-phenyl-1, 3,4-oxadiazole, yield: 82%, mp: 199-200 ° C. |
81% | With acetic acid at 20℃; for 5h; | |
81% | With chloramine-T In ethanol for 3h; Reflux; | |
80% | With potassium bromate; oxalic acid; potassium bromide at 20℃; for 0.333333h; | |
77.6% | With bromine; anhydrous Sodium acetate; acetic acid for 0.00416667h; Microwave irradiation; Heating; | |
71% | With bromine; anhydrous Sodium acetate In acetic acid at 20℃; for 0.5h; | |
65% | With bromine; acetic acid for 0.5h; | |
60.3% | With bromine; anhydrous Sodium acetate for 1h; Heating; | |
57% | With N-Bromosuccinimide; anhydrous Sodium acetate; acetic acid at 25 - 110℃; for 0.25h; Sonication; | General procedure for the preparation of 2-amino-1,3,4-oxadiazoles under ultrasound conditions General procedure: Semicarbazone 1 (1 mmol), NBS (0.196 g, 1.1 mmol), and sodium acetate (0.090 g,1.1 mmol) were mixed in acetic acid (20 mL) in a 50-mL beaker. The reaction mixture was sonicated for 15 min using an ultrasonic probe. Afterward, the resulting solution was poured into cool water and the solid obtained was filtered and washed with water. Finally,the product was dried under reduced pressure. Compounds 2e and 2m did not precipitate and were extracted from water with chloroform (3 15 mL). The products were isolated in satisfactory purity. 5-Phenyl-1,3,4-oxadiazol-2-amine (2a): yield 62%; mp: 238-239 °C (mp: 242-243 °C)[27];HPLC 97% (tR 14.50 min); 1H NMR (400 MHz, DMSO-d6) δ ppm 7.28 (br, 2H, NH2),7.53-7.55 (m, 3H, Ph), 7.82-7.84 (m, 2H, Ph); 13C NMR (100 MHz, DMSO-d6) δ ppm124.4, 125.0, 129.1, 130.3, 157.3, 163.9; (13C NMR (100 MHz, DMSO-d6) δ 124.8, 125.4,129.6, 130.8, 157.7, 164.3)[27]; FTMS (ESI) m/z 162.0654 [MH]; calcd for C8H7N3O:162.0662. |
With sodium hypobromide | ||
With iodine; anhydrous sodium carbonate; potassium iodide | ||
With bromine; anhydrous Sodium acetate In acetic acid | ||
With bromine; anhydrous Sodium acetate In acetic acid | ||
With bromine; anhydrous Sodium acetate; acetic acid | ||
With bromine; anhydrous Sodium acetate In acetic acid | ||
With bromine; anhydrous Sodium acetate In acetic acid for 1h; | ||
With bromine; anhydrous Sodium acetate In acetic acid for 1h; | ||
With bromine; anhydrous Sodium acetate; acetic acid Heating; | ||
With bromine; anhydrous Sodium acetate; acetic acid for 1h; Warming; | ||
With bromine; anhydrous Sodium acetate; acetic acid at 20℃; | ||
With bromine; anhydrous Sodium acetate; acetic acid | ||
78 mg | With iodine; potassium carbonate In 1,4-dioxane at 80℃; | |
With bromine; anhydrous Sodium acetate; acetic acid at 20℃; for 2h; | 1 General procedure: A solution of bromine (0.38 mL, 0.01 mol) diluted with acetic acid (2 mL) was added to a mixture of C1-C2 (8.0 mmol) and sodium acetate (0.82 g, 0.01 mol) in acetic acid (10 mL) at rt. for2 h. The reaction mixture was poured into ice-water (10 mL). The resulting precipitate was filtered and dried under reduced pressure to afford D1-D2 as light yellow solid. | |
With sodium hypoiodite In water monomer at 80 - 85℃; | Synthesis of 5-substituted-1,3,4-oxadiazol-2-amines (4a-j) General procedure: To an aqueous solution of semicarbazidehydrochloride (1:1g) and sodium acetate (8:2g),substituted benzaldehydes (1a-j) (0.02 mol) in 15 mlof ethanol were added by stirring, stirring wascontinued for another 15-30 min then the mixture waskept aside undisturbed for 1 hr and the obtainedprecipitate was collected and purified byrecrystallization from ethanol.The prepared semicarbazones (3a-j) (0.005 mol)were heated with stirring at 80-85 0 with water andsodium hypoiodate (NaOI) solution for 4-5 hr, thereaction mixture was cooled and the precipitate wascollected and recrystallized from ethanol. | |
With bromine; anhydrous Sodium acetate; acetic acid at 60℃; for 1h; | ||
With bromine; anhydrous Sodium acetate In acetic acid at 60℃; for 3h; | Step 2: General procedure: To a vial was added the imine formed in Step 1 (1.0 eq.), sodium acetate (2.0 eq.) and acetic acid (0.5 mL). To a second vial was added the bromine (1.1 eq.) in acetic acid (0.5mL). The bromine solution was then added to the first vial while stirring in a dropwise manner at room temperature. The reaction was then heated to 60°C and stirred for 3^h. The reaction was then cooled to room temperature and poured onto ice water. A yellow precipitate formed and was filtered by vacuum filtration then rinsed with DCM to provide the corresponding 1,3,4-oxadiazolyl amine. | |
With bromine; anhydrous Sodium acetate; acetic acid | 4.1.5. General procedure for the preparation of 5-substitutedphenyl oxadiazole2-amine (8a-d) General procedure: To the solution of 2-Substituted benzylidene hydrazine carbox- amide (0.01 M) (7a-d) and sodium acetate (0.02 M) dissolved in 10 ml glacial acetic acid under stirring, 5 ml of bromine in glacial acetic acid (0.7 ml bromine in 5ml of GAA) was added slowly drop wise. The stirring was continued for 3-6 hours. The progress and completion was monitored by TLC. After completion the mixture was poured into the crushed ice. The solid obtained was filtered, washed with water and dried to get compound (8a-d) . | |
With bromine; anhydrous Sodium acetate In acetic acid at 20℃; | General procedure: Semicarbazide (5 mmol) and water (50 mL) were added into a 250 mL flask and stirred to dissolve. Then aromatic aldehyde (5 mmol) and ethanol (20 mL) were added and the mixture was stirred under reflux reaction for 3 h to give crude 5. This crude product was recrystallized from ethanol to give the pure product 5. Compound 5 (3 mmol), anhydrous sodium acetate (6 mmol) and glacial acetic acid (12 mL) were added into a 100mL flask and stirred to dissolve, then the mixture of bromine (0.6 mL) and glacial acetic acid (2 mL) were slowly added to stir at room temperature. After completion of the reaction, the mixture was poured into ice-water (100 mL) to give white precipitate, filtered and recrystallized from ethanol to give compound 6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With hydrogenchloride; sodium nitrite at 0 - 5℃; | |
With hydrogenchloride; sodium nitrite | ||
(nitrosation); |
With hydrogenchloride; sodium nitrite In water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | In toluene for 6h; Reflux; | 4.1.2. General procedure for the preparation of 2-phenylimidazo[2,1-b][1,3,4]oxa/thiadiazol-5,6-dione 7a-d General procedure: To a suspension of the appropriate oxa/thiadiazole 5a-d (10 mmol) in toluene (40 mL) at 60-65 °C, oxalyl chloride (15 mmol, 1.90 g, 1.27 mL) added dropwise with stirring, then refluxed for 6 h. The solid product separated on cooling was filtered, washed twice with 15% potassium carbonate solution (20 mL), dried, and crystallized from methanol. |
In benzene |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | for 48h; Reflux; | 5 7-Methyl-2-phenyl-5H-[1,3,4]oxadiazolo-[3,2-a]pyrimidine-5-one (3) 10 g (62 mmol) of 2 and 40 ml (317 mmol) ethyl acetoacetate were refluxed for 48 h. The excess ethyl acetoacetate was evaporated and the crude product was purified by chromatography on silica gel column. Elution with ethyl acetate/hexane (70:30) gave 4 g (30%) of 3. Mp: 179-180 °C; IR: (KBr) ν (cm-1)1698, 1632, 1607; mass m/z (%): 227 (M+, 9), 143 (10), 110 (29), 105 (100), 103 (37), 77 (100); 500 MHz 1H NMR (CDCl3): δ ppm: 2.46 (3H, s, CH3), 6.32 (1H, s, H-C6 of oxadiazolopyrimidinone ring), 7.61 (2H, t, J = 7.5 Hz, H3 & H5 of phenyl ring), 7.70 (1H, t, J = 7.5 Hz, H4 of phenyl ring), 8.18 (2H, d, J = 7.5 Hz, H2 & H6 of phenyl ring). Anal. Calcd for C12H9N3O2: C, 63.43; H, 3.99; N, 18.49. Found: C, 63.30; H, 4.03; N, 18.56. |
at 180℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.1% | In ethanol Microwave irradiation; | |
58% | With acetic acid In ethanol Reflux; | 4.1.8. General procedure for the preparation of (XIIa,b, XVIIa,b andXVIIIa-c) General procedure: To a solution of compound VIII or XIIIa,b (10 mmol) and theappropriate aldehyde (10 mmol) in absolute ethanol, drops ofglacial acetic acid were added. The reaction mixture was refluxedfor 14e20 h and the formed precipitate was filtered off while hot.The obtained solid was then re-crystallized from ethanol. |
With toluene-4-sulfonic acid In toluene Heating; |
In ethanol Reflux; | ||
In ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.1% | In ethanol Microwave irradiation; | |
90% | In ethanol for 4h; Heating; | |
at 160 - 170℃; |
In ethanol | ||
With acetic acid In methanol Heating; | ||
In ethanol Reflux; | ||
In ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With triethylamine In ethanol for 10h; Reflux; | 4.1.5. General procedure for preparation of (IX, XIVa,b) General procedure: A mixture of VIII or XIIIa,b (1.97 mmol) and phenylisocyanate(2.37 mmol) in absolute ethanol with few drops of triethylaminewas refluxed for 10 h. The formed precipitate was filtered off andre-crystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium carbonate In dichloromethane at 10℃; | General procedure for 2-chloro-N-(5-substituted-aryl-1,3,4-oxadiazol-2-yl)acetamide (5a-l) The obtained compounds (4a) (2.57 g; 0.016 moles) weredissolved in DCM (30 ml), and to this solution, powderedanhydrous K2CO3 (1 g) was added. Chloroacetyl chloride(2.38 ml; 0.03 mole) was added dropwise with constantstirring to the reaction mixture maintained at 10 °C in anice-water bath. The reaction mixture was stirred continuouslyfor another 2-4 h. After stirring, it was left openovernight so that excess DCM left over the reaction mixturegets evaporated. After that water was added to the residueand stirred for another 20 min. The crude precipitateobtained was filtered, washed twice or thrice with water,and then dried (5a) yield of 92%. The obtained product wasrecrystallized from ethanol. The purity and progress of thereaction were checked throughout by TLC using toluene:ethyl acetate: formic acid (TEF) (5:4:1) as mobile phase[26]. Other derivatives 5b-l were similarly synthesized. |
92% | With potassium carbonate In dichloromethane at 10℃; | General procedure for 2-chloro-N-(5-substituted-aryl-1,3,4-oxadiazol-2-yl)acetamide (5a-l) The obtained compounds (4a) (2.57 g; 0.016 moles) weredissolved in DCM (30 ml), and to this solution, powderedanhydrous K2CO3 (1 g) was added. Chloroacetyl chloride(2.38 ml; 0.03 mole) was added dropwise with constantstirring to the reaction mixture maintained at 10 °C in anice-water bath. The reaction mixture was stirred continuouslyfor another 2-4 h. After stirring, it was left openovernight so that excess DCM left over the reaction mixturegets evaporated. After that water was added to the residueand stirred for another 20 min. The crude precipitateobtained was filtered, washed twice or thrice with water,and then dried (5a) yield of 92%. The obtained product wasrecrystallized from ethanol. The purity and progress of thereaction were checked throughout by TLC using toluene:ethyl acetate: formic acid (TEF) (5:4:1) as mobile phase[26]. Other derivatives 5b-l were similarly synthesized. |
79% | In toluene for 12h; Inert atmosphere; Reflux; | 2-Chloro-N-(5-phenyl-1,3,4-oxadiazol-2-yl)acetamide (4). To a cold (0 oC) solution of 0.331 g (2.05mmol) of compound 2B in 10 mL of toluene under argon, was added 0.2 mL (2.47 mmol) of chloroacetyl chloride and the solution was stirred under reflux for 12 h. The reaction solution was cooled to 25 oC,concentrated on a rotary evaporator, and column chromatographed on silica gel using a gradient mixture of CH2Cl2 and MeOH as eluent to give 0.385 g, 79% yield of compound 4. 1H NMR (DMSO-d6): 12.35 - 12.18 (bs, 1H), 8.02 - 7.82 (m, 2H), 7.72 - 7.47 (m, 3H), 4.46 (s, 2H) ppm. 13C NMR(DMSO-d6): 164.5, 160.7, 157.0, 131.9, 129.6, 126.1, 123.3, 43.2 ppm. MS (positive mode): m/z calcd for C10H8ClN3O2Na (M+Na)+: 260.6, found 260.4; and C10H9ClN3O2+ (M+H)+: 238.65, found 238.2 (100%). |
In benzene | ||
Stage #1: 5-phenyl-[1,3,4]-oxadiazol-2-ylamine With potassium carbonate In dichloromethane; N,N-dimethyl-formamide at 20℃; Stage #2: chloroacetyl chloride In dichloromethane; N,N-dimethyl-formamide Cooling with ice; | 1.2 (2) preparation method of 2-chloro-N-(5-phenyl-1,3,4-oxadiazole)acetamide A 100 mL round bottom flask was charged with 2-amino-5-phenyl-1,3,4-oxadiazole (2.48 mmol), potassium carbonate (7.45 mmol), and 30 mL of N,N-dimethylformamide. After stirring at room temperature until 2-amino-5-phenyl-1,3,4-oxadiazole was completely dissolved,then added 15~20 mL of dichloromethane, stirred at room temperature for 0.5 to 1 hour, slowly added chloroacetyl chloride (7.45 mmol) under ice bath, and the reaction was carried out for overnight. After the dichloromethane was spin-dried, the reaction mixture was poured into ice water to give 22-chloro-N-(5-phenyl-1,3,4-oxadiazole)-acetamide, which was directly subjected to the next reaction without purification. | |
In N,N-dimethyl-formamide at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With potassium carbonate In benzene at 70℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With potassium hydroxide for 5h; Heating; | |
Stage #1: ethanol; 2-amino-5-phenyl-1,3,4-oxadiazole With potassium hydroxide for 5h; Reflux; Stage #2: With acetic acid In water | 3 General procedure: A solution of D1-D2(6.0 mmol), KOH (1.0 g, 0.02 mol) in EtOH was heated at reflux for 5 h. Upon cooling to rt., the solvent was removed under vacuum,and H2O (5 mL) was added to the mixture. The solution was adjusted to pH 4-5 with HOAc, and then the resulting precipitate was filtered and dried under reduced pressure to obtain white solid E1-E2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With potassium hydroxide In N,N-dimethyl-formamide at 120 - 130℃; for 7h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With triethylamine In pyridine for 1h; Heating; | |
75% | With pyridine; triethylamine for 1h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In ethanol for 4h; Heating; | |
54% | With acetic acid In ethanol Reflux; | 4.1.8. General procedure for the preparation of (XIIa,b, XVIIa,b andXVIIIa-c) General procedure: To a solution of compound VIII or XIIIa,b (10 mmol) and theappropriate aldehyde (10 mmol) in absolute ethanol, drops ofglacial acetic acid were added. The reaction mixture was refluxedfor 14e20 h and the formed precipitate was filtered off while hot.The obtained solid was then re-crystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With triethylamine In benzene at 70℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With pyridine at 0℃; | N-(5-Phenyl-1,3,4-oxadiazol-2-yl)-benzamide (2d) Benzoyl chloride (3.68mL, 0.032mol) was added dropwise into the stirred slurry of compound 2-amino-5-phenyl-1,3,4-oxadiazole (5.64g, 0.035mol) in 50mL pyridine. After 2h, the solution was poured into ice-water; and the white precipitate formed was collected and dried under vacuum. Pure product was obtained by re-crystallization from ethanol, mp 203-205°C. Yield: 6.28g, 74%. 1H NMR (DMSO, 300MHz) δ/ppm: 7.55-8.05 (m, 10 H), 12.14 (s, 1H). 13C NMR (DMSO, 300MHz): δ/ppm: 165.18, 161.43, 158.14, 133.20, 132.39, 132.00, 129.70, 128.84, 128.45, 126.29, 123.59. IR (KBr): 1713, 1618, 1582, 1391, 1293, 1245, 1023, 694cm-1. HRMS (ESI+) calcd. for C15H12N3O2 [M+H]+ 266.0929, found 266.0923. |
74% | With pyridine; dmap at 60℃; for 12h; | Under anhydrous anaerobic conditions,1.0 mmol of benzoyl chloride in pyridine (1 mL) was slowly added dropwise to a solution containing 1.0 mmol2-amino-5-phenyl- [1,3,4] -oxadiazole and 0.1 mmol of DMAP in pyridine (3 mL)Refueling bath at 60 reaction 12h.Reaction finished,The solution was poured into 200 mL of cold water,Consider,Recrystallization from ethanol,To a solution of 2- (N-benzoyl) -amino-5-phenyl- [1,3,4] -oxadiazole (L1) as a white solid. |
49% | In dimethyl sulfoxide at 30℃; for 5h; |
With pyridine; dmap |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | With triethylamine In ethanol at 30℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With potassium hydroxide In N,N-dimethyl-formamide at 100℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With triethylamine In benzene for 2h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With potassium carbonate In benzene at 70℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With thionyl chloride In benzene for 2h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | In toluene for 48h; Dean-Stark; Reflux; | 4.1. Synthesis of diethyl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)(aryl)methyl]phosphonate (4) The synthesis of 4 required, in a first step the preparationof (E)-1-(4-fluorophenyl)-N-(5-phenyl-1,3,4-oxadiazol-2-yl)methanimine. In a round bottomedflask equipped with a Dean Stark apparatus, a mixtureof phenyl-1,3,4-oxadiazol-2-amine (2.0 mmol)and 4-fuorobenzaldehyde (3.0 mmol) in toluene(20 mL) was refluxed for 48 h. After cooling toroom temperature, the solvent was evaporated andthe crude product was washed with cool ethanol(15 mL), filtered and dried under vacuum to affordthe desired imine in yield 75% (0.401 g) as a whitesolid. 1H NMR (300 MHz, DMSO-d6): ± 9.36 (s,1H, NCH), 8.22 (d, 1H, arom. CH, 3 J 8.7 Hz), 8.20(d, 1H, arom. CH, 3 J 8.7 Hz), 8.08-8.05 (m, 2H,arom. CH), 7.66-7.60 (m, 3H, arom. CH), 7.49 (d,1H, arom. CH, 3 J 8.7 Hz), 7.46 (d, 1H, arom. CH,3 J 8.7 Hz) ppm; 13C{1H} NMR (126 MHz, DMSOd6):± 168.91 (s, NCH), 166.11 (s, arom. CquatC(N)N), 165.64 (d, arom. Cquat CF, 1 JCF 254.4 Hz),162.83 (s, arom. Cquat C(Ph)N), 133.09 (d, arom.CH, 3 JCF 9.7 Hz), 132.08 (s, arom. CH of C6H5),131.10 (d, arom. Cquat of C6H4F, 4 JCF 3.9 Hz),129.48 (s, arom. CH of C6H5), 126.42 (s, arom. CHof C6H5), 123.54 (s, arom. Cquat of C6H5), 116.67(d, arom. CH, 2 JCF 22.3 Hz) ppm; 19F{1H} NMR(282 MHz, DMSO-d6): ± 103.79 (s, CF) ppm. Elementalanalysis calcd. (%) for C15H10ON3F (267.26):C 67.41, H 3.77, N 15.72; found C 67.46, H 3.74N 15.67. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With pyrene; TEA In acetonitrile for 1h; UV-irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid for 2h; Heating; | ||
Stage #1: hydrazine carboxamide; benzoic acid With trichlorophosphate Reflux; Stage #2: With sodium hydrogencarbonate | 4.1. General procedure for the synthesis of 2-amino-5-aryl-1,3,4-oxadiazoles (2a-g) General procedure: A mixture of substituted aromatic acid (1a-g) (0.1 mmol) with semicarbazide (0.01 mmol) in phosphorous oxychloride (15 ml) was refluxed over a steam bath for 5-6 h. The progress of reaction was monitored by TLC using ethyl acetate: acetone (9:1) as eluent. The reaction mixture was cooled and poured on to crushed ice (200 g) with continuous stirring. The solid mass separated was neutralized with sodium bicarbonate solution (10% W/V). The resulted solid thus obtained was collected by filtration, washed well with cold water, dried in vacuum and recrystallized from ethanol. The compounds are already reported previously [30] and [31]. | |
In neat (no solvent) Sonication; |
With sulfuric acid Sonication; | Substituted oxadiazoles and thiadiazoles. General procedure: A mixture of substituted benzoic acid (2 g) and 2 g of semicarbazide or thiosemicarbazide was dissolved in 10 mL of H2SO4and subjected to ultrasonication for 30-45 min at room temperature (TLC). The product obtained was cooled down and poured onto crushed ice. The residue thus obtained was separated, washed with water, recrystallized from ethanol and chromatographed with hexane : ethyl acetate to get the corresponding pure product (Scheme 1) | |
With trichlorophosphate Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With hydrogenchloride; hydrogen In methanol at 20℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | Stage #1: benzoyl chloride; hydrazine carboxamide With sodium acetate; sodium hydrogencarbonate In water Stage #2: With sulfuric acid at 20℃; for 2h; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | Stage #1: ethyl 2-cyanoacetate; 2-amino-5-phenyl-1,3,4-oxadiazole With ammonium acetate at 150℃; for 3h; Stage #2: In 1,4-dioxane for 3h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone at 80 - 90℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 45 percent / dioxane / 16 h / Heating 2: 100 percent / dioxane / 4 h / Heating 3: 92 percent / 70percent aq. H2SO4 / 0.5 h / Heating 4: 1-hydroxybenzotriazole / H2O; dimethylformamide / 15 h / Ambient temperature 5: HCO2H / Pd black / methanol; dimethylformamide / 1.5 h / Ambient temperature | ||
Multi-step reaction with 4 steps 1: 70 percent / dioxane / 22 h / Heating 2: 92 percent / 70percent aq. H2SO4 / 0.5 h / Heating 3: 1-hydroxybenzotriazole / H2O; dimethylformamide / 15 h / Ambient temperature 4: HCO2H / Pd black / methanol; dimethylformamide / 1.5 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 40 percent / dioxane / 16 h / Heating 2: 100 percent / dioxane / 4 h / Heating 3: 85 percent / 70percent aq. H2SO4 / 0.5 h / Heating 4: 1-hydroxybenzotriazole / H2O; dimethylformamide / 15 h / Ambient temperature 5: HCO2H / Pd black / methanol; dimethylformamide / 1.5 h / Ambient temperature | ||
Multi-step reaction with 4 steps 1: 78 percent / dioxane / 22 h / Heating 2: 85 percent / 70percent aq. H2SO4 / 0.5 h / Heating 3: 1-hydroxybenzotriazole / H2O; dimethylformamide / 15 h / Ambient temperature 4: HCO2H / Pd black / methanol; dimethylformamide / 1.5 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 45 percent / dioxane / 16 h / Heating 2: 100 percent / dioxane / 4 h / Heating 3: 92 percent / 70percent aq. H2SO4 / 0.5 h / Heating 4: 1-hydroxybenzotriazole / H2O; dimethylformamide / 15 h / Ambient temperature 5: HCO2H / Pd black / methanol; dimethylformamide / 1.5 h / Ambient temperature | ||
Multi-step reaction with 4 steps 1: 70 percent / dioxane / 22 h / Heating 2: 92 percent / 70percent aq. H2SO4 / 0.5 h / Heating 3: 1-hydroxybenzotriazole / H2O; dimethylformamide / 15 h / Ambient temperature 4: HCO2H / Pd black / methanol; dimethylformamide / 1.5 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 40 percent / dioxane / 16 h / Heating 2: 100 percent / dioxane / 4 h / Heating 3: 85 percent / 70percent aq. H2SO4 / 0.5 h / Heating 4: 1-hydroxybenzotriazole / H2O; dimethylformamide / 15 h / Ambient temperature 5: HCO2H / Pd black / methanol; dimethylformamide / 1.5 h / Ambient temperature | ||
Multi-step reaction with 4 steps 1: 78 percent / dioxane / 22 h / Heating 2: 85 percent / 70percent aq. H2SO4 / 0.5 h / Heating 3: 1-hydroxybenzotriazole / H2O; dimethylformamide / 15 h / Ambient temperature 4: HCO2H / Pd black / methanol; dimethylformamide / 1.5 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: anhydrous Sodium acetate / water monomer / 20 °C 2: bromine; anhydrous Sodium acetate / acetic acid / 0.5 h / 20 °C | ||
Multi-step reaction with 2 steps 1: anhydrous Sodium acetate / ethanol; water monomer / Heating 2: bromine; anhydrous Sodium acetate; acetic acid / Heating | ||
Multi-step reaction with 2 steps 1: anhydrous Sodium acetate / ethanol; water monomer / Warming 2: bromine; anhydrous Sodium acetate; acetic acid / 1 h / Warming |
Multi-step reaction with 2 steps 1: sodium hydroxide / ethanol; water monomer / 1.5 h / 65 °C / pH 7 2: bromine; anhydrous Sodium acetate; acetic acid / 20 °C | ||
Multi-step reaction with 2 steps 1: anhydrous Sodium acetate 2: bromine; acetic acid / 0.5 h | ||
Multi-step reaction with 2 steps 1: anhydrous Sodium acetate / water monomer; methanol / 0.17 h / 20 °C 2: potassium carbonate; iodine / 1,4-dioxane / 80 °C | ||
Multi-step reaction with 2 steps 1: anhydrous Sodium acetate / ethanol; water monomer / 4 h / 20 °C 2: anhydrous Sodium acetate; acetic acid; bromine / 7 h / 20 °C | ||
Multi-step reaction with 2 steps 1: anhydrous Sodium acetate / ethanol / 1 h / 20 °C 2: anhydrous Sodium acetate; acetic acid; bromine / 5 h / 20 °C | ||
Multi-step reaction with 2 steps 1: anhydrous Sodium acetate / water monomer; methanol / 2 h / 20 °C 2: anhydrous Sodium acetate; acetic acid; bromine / 2 h / 20 °C | ||
Multi-step reaction with 2 steps 1: anhydrous Sodium acetate / ethanol / 2 h / 79 °C 2: anhydrous Sodium acetate; N-Bromosuccinimide; acetic acid / 0.25 h / 25 - 110 °C / Sonication | ||
Multi-step reaction with 2 steps 1: anhydrous Sodium acetate 2: chloramine-T / ethanol / 3 h / Reflux | ||
Multi-step reaction with 2 steps 1: anhydrous Sodium acetate / water monomer; ethanol 2: sodium hypoiodite / water monomer / 80 - 85 °C | ||
Multi-step reaction with 2 steps 1: anhydrous Sodium acetate / water monomer; methanol / 0.5 h / 20 °C 2: anhydrous Sodium acetate; bromine / acetic acid / 3 h / 60 °C | ||
Multi-step reaction with 2 steps 1: anhydrous Sodium acetate / methanol; water monomer / 0.5 h / 20 °C 2: anhydrous Sodium acetate; bromine; acetic acid / 1 h / 60 °C | ||
Multi-step reaction with 2 steps 1: anhydrous Sodium acetate / methanol; water monomer 2: acetic acid; bromine; anhydrous Sodium acetate | ||
Multi-step reaction with 2 steps 1: water monomer; ethanol / 3 h / Reflux 2: anhydrous Sodium acetate; bromine / acetic acid / 20 °C | ||
Multi-step reaction with 2 steps 1: anhydrous Sodium acetate 2: anhydrous Sodium acetate; acetic acid; bromine |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | General procedure: 60percent Sodium hydride (w/w) in mineral oil (0.0015 mol) was added to a mixture of appropriate III (0.001 mol) in THF (15 ml) under the condition of inert atmosphere using N2 flow at 5°C. The reaction mixture was kept for 1 h at room temperature. A solution of 2-(methylsulfonyl)-5-pyrimidinecarboxylic acid, ethyl ester (0.0015 mol) in THF (15 ml) was slowly added to reaction mixture. The resulting reaction mixture was stirred for 2-3 h at 5°C. The distilled water (20 ml) was added. The reaction mixture was extracted (10 ml x 3) with dichloromethane. The separated organic layer was dried over MgSO4, filtered, and the solvent was evaporated under reduced pressure to obtain crude product, recrytallized by ethyl acetate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; copper; sodium nitrite; In water; at 55℃; for 0.333333h;Cooling with ice; | General procedure: Compound 2a-g (10 mmol) were ground with an excess of NaNO2 (1.59 g, 30 mmol) and the mixture was introduced in small portions and with stirring into a ice cooled solution of conc. HCl (30 ml) and water (13 ml), containing Cu powder (0.45 g). The reaction mixture was allowed to reach room temperature and heated to 55 C for 20 min. The reaction mixture was cooled and extracted with 30 ml CHCl3 (three times). The combined extracts were washed with NaHCO3 solution, dried over Na2SO4 and evaporated to give crude. The product was crystallized from ethanol. The compounds were characterized by IR (cm-1, KBr) 1624-1590 (CN stretch), 1274-1229 (aryl-C-O-C-assym. stretch), 1065-1025 (aryl-C-O-C-sym. stretch), 690-671 (C-Cl). Mass spectra of compound 3a exhibited molecular ion peak at m/z 180 (M+), other important fragment were observed at 182 (M+ + 2). Compound 3a is already reported previously [32]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With potassium carbonate In toluene for 8h; Reflux; | 4.1.1. General procedure for the preparation of 2-phenylimidazo [2,1-b][1,3,4]oxa/thiadiazol-6(5H)-one (6a-d) General procedure: A mixture of 5a-d (10 mmol) and chloroacetyl chloride (15 mmol, 1.69 g, 1.20 mL) was refluxed in dry toluene (30 mL) in the presence of anhydrous potassium carbonate (1.37 g, 10 mmol) for 8 h. The reaction mixture was then filtered while hot and the filtrate was evaporated to dryness under vacuum. The residual mass was washed with water, dried and crystallized from aqueous ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With triethylamine In ethanol for 12h; Reflux; | 4.1.3. General procedure for the preparation of 2-phenyl-8aH-[1,3,4]oxa/thiadiazolo[3,2-a]pyrimidine-5,7-diamine 8a-d General procedure: A mixture of 5a,b (5 mmol), malononitrile (5 mmol, 0.33 g) and triethylamine (2 mL) in absolute ethanol (30 mL) was heated under reflux for 12 h. The precipitate formed was filtered, dried and crystallized from acetic acid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With acetic acid In water Heating; | General procedure for synthesis of 1-[5-(4-substitutedphenyl)-1,3,4-oxadiazol-2-yl]-urea IV(a-j) General procedure: The appropriate 2-amino-5-aryl-1,3,4-oxadiazole III (a-j) (0.01 mol) was dissolved in 10-30 ml of glacial acetic acid diluted to 50 ml with distilled water. In some cases mixture was warmed to dissolve III (a-j). To this equimolar (0.01 mol) quantity of sodium cyanate in 20-30 ml of warm water was added with stirring. The reaction mixture was allowed to stand several h followed by cooling on an ice bath. The precipitates obtained were collected by filtration, washed with cold water and recrystallized from 90% aqueous ethanol. |
With acetic acid In water for 0.5h; Warming; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.8% | Stage #1: 2-amino-5-phenyl-1,3,4-oxadiazole With n-butyllithium In tetrahydrofuran; hexane at -72℃; for 1h; Inert atmosphere; Stage #2: 2-(chloroseleno)benzoyl chloride In tetrahydrofuran; hexane at 20℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54.9% | Stage #1: 2-amino-5-phenyl-1,3,4-oxadiazole With sodium hydride In tetrahydrofuran at 0 - 20℃; for 0.5h; Stage #2: (4S)-phenyl 7-(3-(trifluoromethyl)phenyl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxylate In tetrahydrofuran | 65.2 Synthesis of (4S)-N-(5-phenyl-l,3,4-oxadiazol-2-yl)-7-(3-(trifluoromethyl)phenyl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide To a solution of amine 5-phenyl-l,3,4-oxadiazol-2-amine (30 mg, 0.18 mmol) in dry THF (5 mL) was added NaH (18 mg, 0.75 mmol) in portions at 0 C, the reaction mixture was stirred at room temperature for 30 min. (4S)-phenyl 7-(3-(trifluoromethyl)phenyl)-3,4- dihydro-l,4-methanopyrido[2,3-b][l,4]diazepine-5(2H)-carboxylate (157 mg, 0.37 mmol)was then added and the mixture was stirred overnight. The resulting mixture was quenched with MeOH (2 mL), concentrated in vacuo by evaporator. The residue was purified by prep-TLC to give 2-(3-((2,2-dimethyl-l,3-dioxolan-4-yl)methyl)phenyl)-4,4,5,5- tetramethyl-l,3,2-dioxaborolane (50 mg, yield 54.9%) as a white solid |
54.9% | Stage #1: 2-amino-5-phenyl-1,3,4-oxadiazole With sodium hydride In tetrahydrofuran at 0 - 20℃; for 0.5h; Stage #2: (4S)-phenyl 7-(3-(trifluoromethyl)phenyl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxylate In tetrahydrofuran | 65.2 Synthesis of (4S)-N-(5-phenyl-1,3,4-oxadiazol-2-yl)-7-(3-(trifluoromethyl)phenyl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide To a solution of amine 5-phenyl-1,3,4-oxadiazol-2-amine (30 mg, 0.18 mmol) in dry THF (5 mL) was added NaH (18 mg, 0.75 mmol) in portions at 0° C., the reaction mixture was stirred at room temperature for 30 min. (4S)-phenyl 7-(3-(trifluoromethyl)phenyl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxylate (157 mg, 0.37 mmol) was then added and the mixture was stirred overnight. The resulting mixture was quenched with MeOH (2 mL), concentrated in vacuo by evaporator. The residue was purified by prep-TLC to give 2-(3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (50 mg, yield 54.9%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With pyridine; dmap at 60℃; for 16h; | |
With pyridine; dmap at 60℃; for 12h; | Under anhydrous anaerobic conditions,1.0 mmol of diphenylphosphinic chloride in pyridine (1 mL)The solution was slowly added dropwise to a solution containing 1.0 mmol2-amino-5-phenyl- [1,3,4] -oxadiazole and0.1 mmol of DMAP in pyridine (3 mL)Refueling bath at 60 reaction 12h.Reaction finished,The solution was poured into 200 mL of cold water,Consider, recrystallize with ethanol,A solution of 2- (N-diphenylphosphoramidyl) -amino-5-phenyl- [1,3,4] -oxadiazole (L2) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In dichloromethane at 20℃; for 8h; | 1.5 step 5 the18.22g (0.05mol) 2- (((3aR, 4R, 6R, 6aR)-5- (9H-Purin-9-yl)- 2,2-dimethyl-tetrahydrofuran [3,4-d][1,3] Dioxolan-4-yl)methylamino) Acetic acid , 8.06g (0.05mol) of 2-amino-5-phenyl-1,3,4-oxadiazoladded into 160ml of dichloromethane , after dissolving added 24.08g(0.075mol)of TBTU and 48ml of triethylamine, at room temperature keep the reaction for8h, completion of the reaction, concentrated, Silica gel (200-300 mesh) columnchromatography purification, eluent is containing 0.3% of Chloroform - methanolof triethylamine, the volume ratio of Chloroform with methanol is 73:1, toobtain 18.49g of 2- (((3aR, 4R, 6R, 6aR)-5- (9H-Purin-9-yl)- 2,2-dimethyl-tetrahydrofuran [3,4-d][1,3] Dioxolan-4-yl)methylamino) -Ν- (5- phenyl-1,3,4-oxadiazol-2-yl) acetamide, Yield: 73%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In dichloromethane at 20℃; for 8h; | 1.5 Steps 5: will 18.27g (0.05mol) 2 - (( (3aR, 4R, 6R, 6aR) - 2,2-dimethyl-6 - (6-oxo -1H-purine -9 (6H)-yl) tetrahydrofuran [3,4-d] [1,3] b oxa cyclopentane-4-yl) methylamino) acetic acid, 8.06g (0.05mol) 2-amino-5-phenyl -1, 3, 4-oxadiazole is added to 120 ml of methylene chloride, is added to be dissolved after 24.08g (0.075mol) TBTU and 14 ml triethylamine, room temperature reflow 8h, after the reaction, concentration, silica gel (200-300 mesh) column chromatography purification, the eluting agent containing 0.3% acetic acid chloroform-methanol, chloroform and volume ratio of methanol 81:1, to obtain 18.49g2 - (( (3aR, 4R, 6R, 6aR) - 2,2-dimethyl-6 - (6-oxo -1H-purine -9 (6H)-yl) tetrahydrofuran [3,4-d] [1,3] b oxa cyclopentane-4-yl) methylamino)-N - (5-phenyl -1, 3, 4-oxadiazol-2-yl) acetamide, yield: 73%, melting point: 171-173°C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With pyridine; manganese(IV) oxide at 110℃; Green chemistry; | 1 2-amino-5-phenyl-1,3,4-oxadiazole 1)To a dry threeneckedflask Amol 2benzylidenesemicarbazide, Bmol dioxide Manganese and CmL pyridine at 110 ° Cunder stirring, the reaction process of the reaction was monitored by TLC until aminals Urea feed point disappears, to obtaina reaction mixture wherein, A: B: C = 1: 1.2: 10 monitored by TLC When used The developer is a mixture of ethyl acetateand petroleum ether made, and the volume ratio of ethyl acetate and petroleum ether 1: 3[2]2)The reaction mixture was cooled to room temperature, vacuum filtration, and the filtrate was concentrated to dryness togive, as a white solid Body, a white solid was washed with water, vacuum filtration to give the crude product, the crudeproduct was recrystallized from anhydrous ethanol 2Amino5phenyl1,3,4oxadiazolepure, yield of 93%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With potassium carbonate In acetonitrile for 5h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With toluene-4-sulfonic acid at 20℃; for 0.25h; | 1 Example 1 To a dry mortar was added 0.005 mol of 3,6-dimethylacyl-9-methylcarbazole, 0.011 mol of 2-amino-5-phenyl-1,3,4-oxadiazole and 0.011 mol P-toluenesulfonic acid, i.e., 3,6-dimethylacyl-9-methylcarbazole: 2-amino-5-phenyl-1,3,4-oxadiazole: p-toluenesulfonic acid 1: 2.2; grinding at room temperature for 15min, at this time TLC monitoring showed 3,6-dicarboxyl-9-methyl carbazole and 2-amino-5-phenyl-1,3,4-oxadiazole raw point disappeared, Indicating that the raw material is completely reacted and then left to stand for 30 min to obtain a mixture; wherein the developing agent is a mixed solvent of ethyl acetate and petroleum ether in a volume ratio of 1: 3;2) The mixture was washed with water to obtain 3,6-dicarboxyl-9-methylcarbazole 2-amino-5-phenyl-1,3,4-oxadiazole Schiff base.Mp: 252.7 to 254.9 ° C in a yield of 88.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With pyridine In dichloromethane at 25℃; for 4h; | 115 5 -Chloro-N-(5 -phenyl- 1,3 ,4-oxadiazol -2-yl)thiophene-2-carboxamide To a solution of 0.20 g (1.24 mmol) of 5-phenyl-1,3,4-oxadiazol-2-amine in 2 mL of DCM at 25 °C, pyridine (1.86 mmol) and 0.22 g (1.24 mmol) of 5-chlorothiophene-2- carbonyl chloride were added. The reaction solution was stirred at 25 °C for 4 h, diluted with 20 mL of aqueous sodium bicarbonate, and extracted three times with DCM. The combined organic layer was washed with brine, dried over anhydrous Na2504, concentrated, and the residue was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexane (1:1) as eluant to give 0.20 g (53% yield) of the title compound as a white solid. ‘HNIVIR (400 MHz, CDC13) ppm 12.3 (d, J= 3.9 Hz, 1H), 8.00 (d, J= 7.4 Hz, 2H), 7.60 - 7.66 (m, 1H), 7.52 - 7.59 (m, 2H), 7.08 (d, J= 4.3 Hz, 1H). MS (ESI) m/z =327.8 (M+Na). |
53% | With pyridine In dichloromethane at 0 - 25℃; for 3.5h; Inert atmosphere; | 5-Chloro-N-(5-phenyl-1,3,4-oxadiazol-2-yl)thiophene-2-carboxamide (11). To a cold (0 oC) solution of 0.30 g (1.86 mmol) of compound 2B and 0.22 g (2.79 mmol) of pyridine in 10 mL of CH2Cl2 under argon, was added a solution of 0.34 g (1.86 mmol) of 5-chlorothiophene-2-carbonyl chloride (17A) in 5mL of CH2Cl2. The resulting mixture was stirred at 25 oC for 3.5 h, diluted with 40 mL of 10% aqueous NaHCO3 solution, and extracted three times with CH2Cl2. The combined extract was washed with brine, dried (anh. Na2SO4), concentrated, and column chromatographed on silica gel using a gradient mixture ofhexane and EtOAc as eluent to give 0.30 g (53% yield) of compound 11. 1H NMR: δ 8.22 (bs, 1H, NH),8.12 (d, J = 4.3 Hz, 1H), 7.98 (d, J = 7.4 Hz, 2H), 7.67 - 7.49 (m, 3H), 7.06 (d, J = 4.3 Hz, 1H) ppm.13C NMR: δ 158.3, 154.3, 151.3, 142.1, 137.3 133.3, 129.9, 129.4, 127.2, 127.1, 122.4 ppm. MS (positive mode): m/z calcd for C13H8ClN3O2SNa (M+Na)+: 328.0, found 327.8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With trichlorophosphate In toluene at 110℃; for 1h; Cooling with ice; | 2.1 Example 2 (1)In a 50 mL dry three-necked flask,Add 20mmol of benzoic acid,20 mmol semicarbazide hydrochloride and 10 mL anhydrous toluene;10 mL of phosphorus oxychloride was added dropwise under ice bath conditions.After the addition was completed, the temperature was raised to 110°C for 1 hour.After the reaction is completed, most toluene and phosphorus oxychloride are evaporated.The remaining oily liquid is added with ice water at room temperature to quench the remaining trichlorinPhosphorus, cooled to room temperature,The pH was adjusted to alkaline (pH 8-10) with 50% sodium hydroxide.Filter to obtain crude 2-amino-5-phenyl-1,3,4oxadiazole,The crude product is dried and recrystallized from methanol/methylene chloride,White needle crystals,Yield 80%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In dichloromethane at 20℃; for 5h; Cooling with ice; | 2.3 Example 2: (3)Another 50mL dry single-mouth flask flask3 mmol of 2-amino-5-phenyl-1,3,4 oxadiazole and 10 mL of dichloromethane were successively added.A solution of 2 mmol of phenazine-1-carbonyl chloride in dichloromethane was added dropwise under ice-cooling. After the addition was completed, the temperature was raised to room temperature for 5 hours. After the reaction is completed,Most of the dichloromethane is distilled off.The remaining solid is recrystallized from dichloromethane/ether,Yellow needle crystals were obtained with a yield of 90%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | Stage #1: 3-benzoyl-4-hydroxybenzoic acid With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dimethyl sulfoxide at 20℃; for 0.333333h; Stage #2: 2-amino-5-phenyl-1,3,4-oxadiazole In dimethyl sulfoxide at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.039 g | With pyridine at 20℃; for 18h; | Step 2: General procedure: To a vial was added the 4A (0.050 g, 0.23 mmol, 1.0 eq.)followed by pyridine (0.3 mL). To the vial containing the 3-trifluoromethylbenzoyl chloride (carried over from previousstep) was add pyridine (0.3 mL) to form a suspension. The acylchloride suspension was added to the first vial while stirring atroom temperature. The reaction stirred for 18 h thenwas pouredinto ice water and a precipitate formed. This precipitate wasfiltered by vacuum filtration and was further purified by normalphase flash chromatography (0-5% MeOH:DCM). All fractionscontaining the desired product were isolated and concentratedto produce 6 (0.14 g, 0.035 mmol, 15%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With pyridine at 20℃; for 18h; | N-(5-phenyl-1,3,4-oxadiazol-2-yl)-4-(isopropoxy)benzamide (67). To a vial was added the 5-phenyl-1,3,4-oxadiazol-2-amine (0.040 g, 0.25 mmol, 1.0 eq.) followed bypyridine (0.6 mL) and 4-isopropoxybenzoyl chloride (0.054 g, 0.27 mmol, 1.2 eq.) at room temperature. Thereaction stirred for 18 hours then was poured into ice water and a precipitate formed. This precipitate was filteredby vacuum filtration and was further purified by reverse-phase flash chromatography (5 - 100% MeCN:water).All fractions containing the desired product were isolated and concentrated to produce 67 (0.028 g, 0.084 mmol,40%) as a pale yellow solid. (0.010 g, 0.031 mmol, 12%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With acetic acid at 150 - 160℃; | Synthesis of 2-(1H-pyrrol-1-yl)-5-substituted-1,3,4-oxadiazoles (5a-j) General procedure: Compounds (5a-j) were synthesized by refluxinga mixture of 5-substituted-1,3,4-oxadiazol-2-amines(4a-j) (2g, 0.1 mol) in dried acetic acid (15 ml) and2,5-dimethoxytetrahydrofuran (1.9ml, 0.12 mol) for 45min to 1 hr at 150-160 0 , the reaction mixture was poured into ice cold water, the solid separated wasfiltered and recrystallized from aq. ethanol.5a: IR (KBr): cm -1 : 2921 (ArH), 1612 (C-O), 1584(C=N). 1 H NMR (400 MHz, CDCl3, δ ppm): 6.43 (dd,2H, C3 & C4-H of pyrrole), 7.43 (dd, 2H, C2 & C5-H ofpyrrole), 7.50-7.57 (t, 3H, C3, C4 & C5-H of phenyl),8.05 (d, 2H, C2 & C6-H of phenyl), 13 C NMR (100 MHz,CDCl3), 108.5 (C3, C4-pyrrole), 114.5 (C2, C5-pyrrole),118.1 (C1-phenyl), 121.7 (C2, C6-phenyl), 124.3 (C4-phenyl), 126.5 (C3, C5-phenyl), 152.2 (C5-oxadiazole),156.5 (C2-oxadiazole). Mass : m/z 212 (M + +1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Stage #1: hydrazinecarboxamide monohydrochloride; benzaldehyde With anhydrous Sodium acetate In methanol; lithium hydroxide monohydrate at 20℃; for 0.333333h; Stage #2: With iodine; potassium carbonate In 1,4-dioxane at 80 - 85℃; | 1.1 (1) preparation method of 2-amino-5-phenyl-1,3,4-oxadiazole A 100 mL round bottom flask was charged with semicarbazide hydrochloride (9.42 mmol) and sodium acetate (9.42 mmol), dissolve it in 20 mL of secondary water, and then slowly added 20 mL of methanol containing benzaldehyde 0.42 mmol, and stirred at room temperature for 20 minutes. The solvent was spin-dried, and 40 mL of 1,4-dioxane, potassium carbonate (28.37 mmol), and Simple substance iodine (10.37 mmol) were added, and the mixture was heated at 80 to 85 ° C for 4 to 6 hours. The reaction was traced by thin layer chromatography until it no longer changed. Poured the reaction into a 25% aqueous solution of sodium thiosulfate, extracted with a mixed solvent of dichloromethane : methanol = 10:1,dried over anhydrous sodium sulfate, spin-dried, carried out recrystallization from N,N-dimethylformamide with dichloromethane to give Intermediate 1 in a yield of 81%. |
68% | Stage #1: hydrazinecarboxamide monohydrochloride; benzaldehyde With anhydrous Sodium acetate In tetrahydrofuran; lithium hydroxide monohydrate for 1.5h; Cooling with ice; Stage #2: With chloramine-T; potassium carbonate In tetrahydrofuran; lithium hydroxide monohydrate at 20℃; for 3h; Reflux; | C2-2 Example C2 Production of 5-phenyl-1,3,4-oxadiazol-2-amine Example C2-2 A solution of semicarbazide hydrochloride (1.22 g, 10.9 mmol) and sodium acetate (0.897 g, 10.9 mmol) in water (10 mL) was cooled in ice, then benzaldehyde (1.11 g, 10.4 mmol) and tetrahydrofuran (THF) (3.0 mL) were added thereto, and the mixture was stirred. 1.5 hours later, tetrahydrofuran (THF) (27 mL), potassium carbonate (3.60 g, 26.0 mmol), and chloramine T trihydrate (4.11 g, 14.6 mmol) were added to the reaction solution, and the mixture was stirred at room temperature. 3 hours later, the reaction solution was washed with a 2:1 mixed solution of a 20% sodium bisulfite aqueous solution and 30% aqueous sodium chloride solution. 4 mol/L hydrochloric acid in ethyl acetate (7.8 mL, 31.2 mol) was added to the obtained organic layer, and the mixture was stirred at room temperature. 30 minutes later, the resulting solid was collected by filtration and washed with tetrahydrofuran (THF). Toluene was added to the filtrate, followed by extraction with a 4:1 mixed solution of 2 mol/L hydrochloric acid and 30% aqueous sodium chloride solution. The solid collected by filtration earlier was added to the obtained aqueous layer, and the mixture was further adjusted to pH 12 or higher by the addition of a 10 mol/L sodium hydroxide aqueous solution. After overnight stirring, the solid was collected by filtration, washed with water, and then dried under reduced pressure to obtain the title compound (1.13 g, yield: 68%) as a white solid. (0263) 1H-NMR (400 MHz, DMSO-D6) δ: 7.81-7.80 (2H, m), 7.56-7.51 (3H, m), 7.27 (2H, brs) (0264) ESI-MS (m/z): 162 (M+H)+ |
With iodine; anhydrous Sodium acetate; potassium carbonate In 1,4-dioxane; methanol; lithium hydroxide monohydrate at 85℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; sodium t-butanolate In N,N-dimethyl-formamide at 110℃; for 36h; Schlenk technique; Inert atmosphere; | General method for preparation 3a-w General procedure: A 10-ml Schlenk tube equipped with a stir-bar was charged with compound 1 (0.2 mmol), compound 2 (0.3 mmol), Pd(OAc)2 (0.02 mmol), Xantphos (0.04 mmol), NaOtBu (0.3 mmol), anhydrous DMF (2 mL).The reaction tube was purged with argon. The Schlenk tube was placed in an oil-bath at 110 oC for 36 hours and then cooled to room temperature. The reaction mixture was extracted with EtOAc (3 × 20 mL). The combined organic phase was dried over MgSO4 and concentrated under reduced pressure and the crude residue purified by flash chromatography on silica gel. The purified material was dried in vacuo to afford the corresponding products 3a-w. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; sodium t-butanolate In N,N-dimethyl-formamide at 110℃; for 36h; Schlenk technique; Inert atmosphere; | General method for preparation 3a-w General procedure: A 10-ml Schlenk tube equipped with a stir-bar was charged with compound 1 (0.2 mmol), compound 2 (0.3 mmol), Pd(OAc)2 (0.02 mmol), Xantphos (0.04 mmol), NaOtBu (0.3 mmol), anhydrous DMF (2 mL).The reaction tube was purged with argon. The Schlenk tube was placed in an oil-bath at 110 oC for 36 hours and then cooled to room temperature. The reaction mixture was extracted with EtOAc (3 × 20 mL). The combined organic phase was dried over MgSO4 and concentrated under reduced pressure and the crude residue purified by flash chromatography on silica gel. The purified material was dried in vacuo to afford the corresponding products 3a-w. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
23% | With palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; sodium t-butanolate; In N,N-dimethyl-formamide; at 110℃; for 36h;Schlenk technique; Inert atmosphere; | General procedure: A 10-ml Schlenk tube equipped with a stir-bar was charged with compound 1 (0.2 mmol), compound 2 (0.3 mmol), Pd(OAc)2 (0.02 mmol), Xantphos (0.04 mmol), NaOtBu (0.3 mmol), anhydrous DMF (2 mL).The reaction tube was purged with argon. The Schlenk tube was placed in an oil-bath at 110 oC for 36 hours and then cooled to room temperature. The reaction mixture was extracted with EtOAc (3 × 20 mL). The combined organic phase was dried over MgSO4 and concentrated under reduced pressure and the crude residue purified by flash chromatography on silica gel. The purified material was dried in vacuo to afford the corresponding products 3a-w. |
23% | With xantphos; palladium diacetate; sodium t-butanolate; In N,N-dimethyl-formamide; at 110℃; for 36h;Schlenk technique; Inert atmosphere; | In a 10 ml Schlenk tube, add compound 1c (51.2 mg, 0.2 mmol), 5-phenyl- [1,3,4]oxadiazole-2-amino (48.3 mg, 0.3 mmol), Pd (OAc) 2 (4.5 mg, 0.02 mmol), xantphos (23mg, 0.04mmol), NaOtBu (29mg, 0.3mmol) and anhydrous DMF (2mL) under the protection of argon,The reaction tube was placed in an oil bath at 110 C. for 36 h for a Buchwald-Hartwig reaction, then cooled to room temperature, and the reaction mixture was extracted with EtOAc (3 × 20 mL). The organic phase was dried over MgSO4 and concentrated under reduced pressure. The corresponding product 2a (17.5 mg) was separated on a silica gel column, white solid, melting point: 180 C, yield 23%, purity 96%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.2% | With triethylamine In N,N-dimethyl-formamide for 0.183333h; Microwave irradiation; | The microwave method General procedure: The 2-Amino-5-aryl-1,3,4-oxadiazole (0.01 mol), α-bromoacetophenones derivatives (0.01 mol) and catalyst were treated by a microwave system for about the appropriate time. The microwave-accelerated reaction system was operated at 200 W. The progress of the reaction was monitored by TLC using dichloromethane/methanol (10:1) as eluent. After completion of the reaction, the solution pH was adjusted to 7-8. The crude product thus obtained was filtered, and recrystallized from N,N-Dimethylformamide to get the compounds (1a-1v). 2,6-Diphenylimidazo[2,1-b][1,3,4]oxadiazole (1a) White solid m.p.: 96-99 °C. IR (KBr) υ: 3042(C-H), 1675(C=N), 1575, 1534, 1476 (Benzene ring), 1089(C-O-C). 1H NMR (DMSO, 400 MHz) δ:7.97(d, 2H, Ar-H), 7.86(d, 2H, Ar-H), 7.75(m,3H, Ar-H), 7.40(m, 2H, Ar-H), 7.32(m, 1H, Ar-H), 7.22(s, 1H, oxadiazole-H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70.6% | In ethanol for 0.416667h; Microwave irradiation; | The microwave method General procedure: The 2-Amino-5-aryl-1,3,4-oxadiazole (0.01 mol), α-bromoacetophenones derivatives (0.01 mol) and catalyst were treated by a microwave system for about the appropriate time. The microwave-accelerated reaction system was operated at 200 W. The progress of the reaction was monitored by TLC using dichloromethane/methanol (10:1) as eluent. After completion of the reaction, the solution pH was adjusted to 7-8. The crude product thus obtained was filtered, and recrystallized from N,N-Dimethylformamide to get the compounds (1a-1v). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70.4% | In ethanol for 0.416667h; Microwave irradiation; | The microwave method General procedure: The 2-Amino-5-aryl-1,3,4-oxadiazole (0.01 mol), α-bromoacetophenones derivatives (0.01 mol) and catalyst were treated by a microwave system for about the appropriate time. The microwave-accelerated reaction system was operated at 200 W. The progress of the reaction was monitored by TLC using dichloromethane/methanol (10:1) as eluent. After completion of the reaction, the solution pH was adjusted to 7-8. The crude product thus obtained was filtered, and recrystallized from N,N-Dimethylformamide to get the compounds (1a-1v). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | In ethanol for 0.166667h; Microwave irradiation; | The microwave method General procedure: The 2-Amino-5-aryl-1,3,4-oxadiazole (0.01 mol), α-bromoacetophenones derivatives (0.01 mol) and catalyst were treated by a microwave system for about the appropriate time. The microwave-accelerated reaction system was operated at 200 W. The progress of the reaction was monitored by TLC using dichloromethane/methanol (10:1) as eluent. After completion of the reaction, the solution pH was adjusted to 7-8. The crude product thus obtained was filtered, and recrystallized from N,N-Dimethylformamide to get the compounds (1a-1v). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.1% | In ethanol for 0.916667h; Microwave irradiation; | The microwave method General procedure: The 2-Amino-5-aryl-1,3,4-oxadiazole (0.01 mol), α-bromoacetophenones derivatives (0.01 mol) and catalyst were treated by a microwave system for about the appropriate time. The microwave-accelerated reaction system was operated at 200 W. The progress of the reaction was monitored by TLC using dichloromethane/methanol (10:1) as eluent. After completion of the reaction, the solution pH was adjusted to 7-8. The crude product thus obtained was filtered, and recrystallized from N,N-Dimethylformamide to get the compounds (1a-1v). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With acetic anhydride for 8h; Heating; | 4.1.7. General procedure for the preparation of (XI, XVIa,b) General procedure: A mixture of compound VIII or XIIIa,b (2 mmol) and catalyticamount of acetic anhydride in excess triethyl orthoformate washeated for 8 h. The reaction mixture cooled and poured onto icewater. The formed precipitate was re-crystallized from ethanol anddried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.8% | With choline chloride; oxalic acid at 70℃; | 10 Example 10 Preparation of 3-formyl-9-methylcarbazole 2-amino-5-phenyl-1,3,4-oxadiazole Schiff base Add 2 g (0.014 mol) of choline chloride, 1.26 g (0.014 mol) of oxalic acid to a dry three-necked flask,Stir at 70 ° C to obtain a colorless transparent solution, namely a eutectic solvent, cool to room temperature, add 502.2mg (2.4mmol) of 3-formyl-9-methylcarbazole,464.1 mg (2.88 mmol) of 2-amino-5-phenyl-1,3,4-oxadiazole was reacted at 70 ° C and monitored by TLC until the reaction was complete.After the reaction, a small amount of water was added to the reaction flask to precipitate a solid, which was filtered by suction, the filter cake was washed with water, dried, and recrystallized.Thus, 3-formyl-9-methylcarbazole 2-amino-5-phenyl-1,3,4-oxadiazole Schiff base was obtained. The water phase can be recovered to recover the eutectic solvent. 85.8% yield, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78.9% | With choline chloride; oxalic acid at 70℃; | 14 Example 14 Preparation of Schiff base of 3,6-diformyl-9-methylcarbazole 2-amino-5-phenyl-1,3,4-oxadiazole Add 2 g (0.014 mol) of choline chloride, 1.26 g (0.014 mol) of oxalic acid to a dry three-necked flask,Stir at 70 ° C to obtain a colorless and transparent solution, namely a eutectic solvent, cool to room temperature, and add 569.4 mg (2.4 mmol) of 3,6-diformyl-9-methylcarbazole.812.3 mg (5.04 mmol) of 2-amino-5-phenyl-1,3,4-oxadiazole was reacted at 70 ° C and monitored by TLC until the reaction was complete. After the reaction, a small amount of water was added to the reaction flask to precipitate a solid, which was filtered by suction, the filter cake was washed with water, dried, and recrystallized.The 3,6-diformyl-9-methylcarbazole 2-amino-5-phenyl-1,3,4-oxadiazole Schiff base is obtained. The water phase can be recovered to recover the eutectic solvent. Yield 78.9%, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | Stage #1: piperic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 5℃; for 0.5h; Stage #2: 2-amino-5-phenyl-1,3,4-oxadiazole In dichloromethane at 20℃; for 2h; | Coupling of piperine with oxadiazoles or thiadiazoles. General procedure: The solution of 2.18 g of piperic acid in 20 mL of anhydrous CH2Cl2 was mixed with 1.92 g of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide HCl (EDC·HCl)and 2.60 mL of N,N-diisopropylethylamine (DIPEA) and stirred at 0-5°C. for 30 min. 1 mol of oxadiazole or thiadiazole derivative was added to the above mixture and stirred at room temperature for 2 h (TLC). After completion of the process (TLC), the reaction mixture was washed with water (2×10 mL), aqueous solution of 1%H3PO4 (2×10 mL), an aqueous solution of 2.5% K2CO3(2×10 mL), and concentrated to give the corresponding crude product. This was purifi ed by column chromatographyusing hexane:ethylacetate as an eluent (Scheme 2).(2E,4E)-5-(Benzo[d][1,3]dioxo-5-yl)-N-(5-phenyl-1,3,4-oxadiazol-2-yl)penta-2,4-dienamide (1). Browncrystals, yield 68%, mp 265°C. IR spectrum, ν, cm-1:1710 (amide CONH), 3100-3500 (amide NH). 1H NMRspectrum, δ, ppm: 5.19 d.d (J = 14.7, 0.8 Hz, 1H), 6.01d (J = 2.3 Hz, 1H), 6.07 d (J = 2.3 Hz, 1H), 6.66 d.d.d(J = 14.0, 7.0, 0.9 Hz, 1H), 6.70-6.82 m (2H), 6.82 d.d(J = 8.5, 1.9 Hz, 1H), 7.04 d (J = 1.8 Hz, 1H), 7.37-7.47m (2H), 7.60-7.50 m (2H), 7.97-7.89 m (2H), 8.21 s(1H). 13C NMR spectrum, δ, ppm: 100.99. 106.96, 108.54,120.68, 123.68, 126.01, 126.65, 126.74, 128.84, 130.40,131.15, 138.30, 140.31, 147.05, 147.90, 152.42, 158.79,168.74. HRMS: m/z: 362.1169 [H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With pyridine at 110℃; for 2h; Irradiation; Microwave irradiation; | 126 Example 126: 5-Ethyl-2-methoxy-N-(5-phenyl-1,3,4-oxadiazol-2- yl)benzenesulfonamide, 126 A suspension of 5-ethyl-2-methoxybenzene-1-sulfonyl chloride 119 (150 mg, 0.639 mmol) and 5-phenyl-1,3,4-oxadiazol-2-amine (103 mg, 0.639 mmol) in pyridine (2 mL) was irradiated in the microwave at 110 °C for 2 hours. The product was purified by column chromatography (0-100% EtOAc in petroleum benzine 40-60 °C) to give the title compound as a white solid (142 mg, 62%). LCMS-C: Rt 6.308 min; m/z 360.1 [M+H]+. 1H NMR (400 MHz, DMSO-de) d 7.88 - 7.80 (m, 2H), 7.71 (d, J = 2.3 Hz, 1H), 7.68 - 7.55 (m, 3H), 7.42 (dd, J = 8.4, 2.3 Hz, 1H), 7.10 (d, J = 8.5 Hz, 1H), 3.72 (s, 2H), 2.63 (q, J = 7.6 Hz, 2H), 1.18 (t, J = 7.6 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15% | With pyridine In dichloromethane at 0 - 25℃; for 2h; Inert atmosphere; | 3-(3-Chlorophenyl)-N-(5-phenyl-1,3,4-oxadiazol-2-yl)propanamide (10). To a cold (0 oC) solution of 0.10 g (0.62 mmol) of 2B in 10 mL of CH2Cl2 under argon, were added 75 L of pyridine and 0.126 g(0.62 mmol) of 3B. The solution was stirred for 2 h, warmed to 25 oC, diluted with 20 mL of aqueous NaHCO3, and extracted three times with CH2Cl2. The combined extract was washed with brine, dried (anhydrous Na2SO4), concentrated, and column chromatographed on silica gel using a gradient mixture of hexane and EtOAc as eluent to give 30 mg (15% yield) of compound 10 as light yellow crystals, mp 201- 203 oC. 1H NMR: δ 8.07 (d, J = 8 Hz, 2H), 7.60 - 7.50 (m, 3H), 7.36 (s, 1H, NH), 7.30 - 7.20 (m, 4H),3.15 - 3.02 (m, 2H), 3.00 - 2.70 (m, 2H) ppm. 13C NMR (DMSO-d6): δ 166.0, 164.1, 155.2, 132.8,133.4, 132.6, 131.1, 130.4, 129.5, 129.2, 128.7, 128.1, 126.9, 35.8, 30.8 ppm. MS (positive mode): m/zcalcd for C17H15ClN3O2 (M+H)+: 329.8, found 330.1 (Cl37 isotope) and 328.0 (Cl35 isotope). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.6% | With benzothiazole ionic liquid In ethanol Reflux; | 4 Example 4 Preparation of 1- (5’-phenyl-1’,3’,4’-oxadiazole-2’-amino) -ethyl-ferrocenyl ketone Add a solution of 2-amino 5-phenyl-1,3,4-oxadiazole (1mol) and 37% formaldehyde (5mol) to the dry three-necked flask, using absolute ethanol as the solvent, and stir well; add benzothiazole ion Liquid (1.2mol), then slowly add acetylferrocene (1mol) absolute ethanol solution, heating and refluxing until the end of the reaction (TLC monitoring), the solvent was distilled off under reduced pressure, ethyl acetate was added to the residue, Suction filtration, the filter cake is benzothiazole ionic liquid, which can be recycled and reused; the filtrate and filtrate are evaporated to obtain the crude product, and the crude product is recrystallized from anhydrous ethanol to obtain 1- (5'-phenyl-1 ', 3', 4 ' -Oxadiazole-2'-amino) -ethyl-ferrocenyl ketone, yield: 92.6%. |
90.7% | With benzimidazole ionic liquid In ethanol Reflux; | 4 Example 4Preparation of 1- (5’-phenyl-1 ’, 3’, 4’-oxadiazole-2’-amino) -ethyl-ferrocenyl ketone Add a solution of 2-amino 5-phenyl-1,3,4-oxadiazole (1 mol) and 37% formaldehyde (5 mol) to a dry three-necked flask, and use absolute ethanol as a solvent.Stir well; add benzimidazole ionic liquid (1.2mol), then slowly add acetylferrocene (1mol) absolute ethanol solution,After dripping, heating and refluxing to the end of the reaction (TLC monitoring), the solvent was distilled off under reduced pressure, ethyl acetate was added to the residue, suction filtration, the filter cake was benzimidazole ionic liquid, which could be recovered and reused; the filtrate was evaporated to dryness ,The crude product is recrystallized from absolute ethanol1- (5’-phenyl-1 ’, 3’, 4’-oxadiazole-2’-amino) -ethyl-ferrocenyl ketone, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; | |
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 16h; | Amide coupling of compounds: General procedure: A 20 mL screw caped vial, charged with the corresponding acid (0.5 mmol), amine (0.5 mmol), BOP reagent (1.4 mmol) and diisopropylethylamine (13 mmol) in anhydrous DMF solvent (3 mL) was stirred at room temperature for 16 h. After completion, the reaction mixture was concentrated under reduced pressure, followed by flash column chromatography (hexanes:ethyl acetate 80:20 to 60:40) give the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With hydrogenchloride; acetic acid In ethanol Reflux; | 4.1.6. General procedure for the preparation of substituted [3-((5-phenyl-1,3,4-oxadiazole-2-yl)imino)indolene-2-one] (5a-f) General procedure: To a solution of 5-substitutedphenyl oxadiazole2-amine (0.01mol) (8a-d) dissolve in absolute ethanol, an equimolar amount of isatin/5-substituted isatin in 5 ml glacial acetic acid and 3-5 drop HCl were added. The reaction mixture was refluxed for 6-8 h. The progress and completion of the reaction was contin- uously monitored by TLC. After completion, the reaction mixtures was poured in crushed ice and solid precipitated was filtered, washed with water, dried and then recrystallized with ethanol to get the final product (5a-f) . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium carbonate In acetone at 20℃; for 10h; | 5,5'-(1,4-Phenylene)bis[1-(2-(5-aryl-1,3,4-oxadiazol-2-yl)thio)acetyl)-3-(2-thienyl)-4,5-dihydro-1H-pyrazole]derivatives (4a-e) / 5,5'-(1,4-Phenylene)bis[1-(2-(5-aryl-1,3,4-oxadiazol-2-yl)amino)acetyl)-3-(2-thienyl)-4,5-dihydro-1H-pyrazole] derivatives (4f-i) General procedure: A mixture of compound 3 (0.005 mol) and 5-aryl-1,3,4-oxadiazole-2-thiol/amine (0.005 mol) in the presence of potassiumcarbonate (0.005 mol) was stirred in acetone (20mL) at room temperature for 10 h. The solvent was evaporated,the residue was washed with water and recrystallizedfrom ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In tetrahydrofuran at 20℃; for 12h; | General procedure: 4-(Chloromethyl)benzoyl chloride (2 mmol), dry tetrahydrofuran (20 mL) and trimethylamine (2 mL) were added into a 100 mL flask and stirred to dissolve. Then the compound 6 (2 mmol) was added to stir at room temperature for 12 h. After completion of the reaction, the mixture was poured into cold water (150 mL). The tetrahydrofuran dissolved in water, then the light yellow precipitate was produced, filtered and dried to give compound 7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With trichlorophosphate for 2h; Reflux; | 4.1.1 General procedure for the synthesis of compound (2a-c) General procedure: A mixture of compounds 1a, 1b or 1c (0.05mol), 2-acetylbutyrolactone (0.05mol) and POCl3 (15mL) was heated under reflux for 2h. then excess POCl3 was distilled under reduced pressure and the residue was triturated with ice water. The obtained suspension was neutralized with 2M ammonia; crude product was filtered, dried, and crystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | Stage #1: 2,4-dibromobutanoyl chloride; 2-amino-5-phenyl-1,3,4-oxadiazole With triethylamine In diethyl ether at 20℃; for 16h; Inert atmosphere; Stage #2: With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 2h; Inert atmosphere; | 4.2.1 General procedure A for amide formation from acyl chloride and cyclization of pyrrolidinone General procedure: To a solution of amine (1 equiv.) in anhydrous diethyl ether (12mL) was added, under inert atmosphere, triethylamine (2 equiv.) followed by a 2,4-dibromobutanoyl chloride (1.1 equiv.). After 16h at room temperature, the solution was filtered, and the filtrate concentrated under reduced pressure. The solvent was evaporated, and the crude product was used in the next step without further purification. A sodium hydride (60 mass%) in mineral oil (1.2-1.5 equiv.) was added to a stirred solution of intermediate (1 equiv.) in tetrahydrofuran at 0°C. The reaction mixture was allowed to warm up to room temperature and stir for an additional 2h. The reaction was carefully quenched with ice and diluted with water. The resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine and water. The organic phase was filtered through a phase separator and concentrated under reduced pressure. Crude product was dry loaded on silica and purified by flash column chromatography to obtain desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | In dichloromethane at 20℃; for 2h; Inert atmosphere; Schlenk technique; | General procedure for the synthesis of the ruthenium(II) complexes 8 and9 General procedure: In a Schlenk tube under argon, [RuCl2(6-p-cymene)]2 (0.061 g, 0.10mmol) and oxadiazole derivative 6 or 7 (0.20 mmol) were introduced.CH2Cl2 (10 mL) was then added and the reaction mixture was stirred atroom temperature for 2 h. After completion of the reaction, the resultingsolution was concentrated to ca. 0.5 mL, upon which n-hexane (10 mL)was added. The orange/red precipitate was separated by filtration,washed with n-hexane and dried under a vacuum. |
Tags: 1612-76-6 synthesis path| 1612-76-6 SDS| 1612-76-6 COA| 1612-76-6 purity| 1612-76-6 application| 1612-76-6 NMR| 1612-76-6 COA| 1612-76-6 structure
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