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CAS No. : | 5202-85-7 | MDL No. : | MFCD00017126 |
Formula : | C7H7ClN2O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | DNRVZOZGQHHDAT-UHFFFAOYSA-N |
M.W : | 170.60 | Pubchem ID : | 78876 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 43.95 |
TPSA : | 69.11 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.69 cm/s |
Log Po/w (iLOGP) : | 0.84 |
Log Po/w (XLOGP3) : | 0.92 |
Log Po/w (WLOGP) : | 1.03 |
Log Po/w (MLOGP) : | 1.18 |
Log Po/w (SILICOS-IT) : | 0.9 |
Consensus Log Po/w : | 0.97 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.81 |
Solubility : | 2.61 mg/ml ; 0.0153 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.96 |
Solubility : | 1.88 mg/ml ; 0.011 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -2.24 |
Solubility : | 0.984 mg/ml ; 0.00577 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.1 |
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 |
---|---|---|
67% | With ytterbium(III) triflate In 1,3,5-trimethyl-benzene at 165℃; for 6 h; Inert atmosphere | General procedure: A mixture of 2-aminobenzamide (1, 4.0 mmol), carboxamide (2, 6.0 mmol), Yb(OTf)3 (0.20 mmol,5.0 molpercent), and mesitylene (5.0 mL) was placed in a 20-mL Pyrex flask equipped with a magnetic stirring bar and a reflux condenser under a flow of argon. The reaction was carried out at 120-165 oC (bath temp.) for 6 h with stirring. Then, the reaction mixture was cooled to room temperature, and analyzed by GLC, GC-MS (EI), and LC-MS (ESI). After evaporation of mesitylene under vacuum,the products (3) were isolated by recrystallization from MeOH/hexane and/or medium pressure column chromatography on silica gel (eluent: EtOAc/hexane = 50/50 ~ EtOAc 100percent. For 3j, eluent:MeOH/CHCl3 = 50/50). 1H NMR spectra were recorded at 400 MHz, and 13C NMR spectra wererecorded at 100 MHz in DMSO-d6. The analytical and spectral data of 3a-e,38 3f,39 3g,40 3h,41 and3j,42 were consistent with those reported previously. The product, 3i, was characterized below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | at 130℃; for 2 h; Inert atmosphere; Microwave irradiation | 2-Amino-5-chlorobenzamide (85 mg, 0.5 mmol), [Cp * Ir (2,2'-bpyO) (H2O)](5.4 mg, 0.005 mmol, 1 molpercent),Cesium carbonate (49 mg, 0.15 mmol, 0.3 equiv.) And methanol (0.5 ml) were sequentially added to a dried 5 mL microwave reaction tube.The tube was nitrogen protected and placed in a single mode pressure microwave synthesizer (Discover CEM, USA). After the reaction mixture was reacted at 130 ° C for 2 hours, it was cooled to room temperature. Rotary evaporation to remove the solvent,Pure target compound was then obtained by column chromatography (developing solvent: petroleum ether / ethyl acetate), yield: 77percent |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.6% | for 16 h; Reflux | General procedure: To a refluxing solution of corresponding anthranilamide (1 mmol) in ethanol (30 mL) was added formamidine acetate (2 mmol). The solution was refluxed for about 6 h (monitored by TLC & LCMS for completion), and solvent evaporated under reduced pressure. The residue was further diluted with water (30 mL) and ethyl acetate (50 mL) and the layers separated. The organic layer was dried over anhydrous sodium sulphate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography using hexane: ethyl acetate as eluent to give the corresponding quinazolin-4(3H)-one (4a-b) in good yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With acetic acid In ethanol at 110℃; for 24 h; Inert atmosphere; Sealed tube | General procedure: The 2-aminobenzamide (1 equiv), the orthoester (2–3 equiv) and absolute ethanol (2–3 mL) wereplaced in a 15-mL Chemglass screw-cap pressure tube (No. CG-1880-01, Chemglass, Vineland, NJ,USA). Glacial acetic acid (3 equiv) was added, N2 was introduced to the vessel and the cap wastightened. The vessel was heated at 110 °C for 12–72 h, then cooled and concentrated to give thequinazolinone, which was purified by crystallization from absolute ethanol or trituration from 5percentether in pentane. The following compounds were prepared: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With ytterbium(III) triflate In 1,3,5-trimethyl-benzene at 60℃; for 24 h; Inert atmosphere | General procedure: 2-aminobenzamide (1, 1.0 mmol), 1,3-diketone (2, 1.5 mmol), Yb(OTf)3 (0.050 mmol, 5.0 molpercent),and mesitylene (2.0 mL) was placed in a 20-mL Pyrex flask equipped with a magnetic stirring bar and a reflux condenser under a flow of argon. The reaction was carried out at 60°C (bath temp.) for 24 h with stirring. The reaction mixture was then cooled to room temperature and analyzed by GLCand GC-MS. The product 3 was isolated by medium-pressure column chromatography on silica gel(eluent: EtOAc/hexane = 30/70 ~ EtOAc 100percent. For 3j, eluent: MeOH/CHCl3 = 30/70 ~ 50/50) andrecrystallization from MeOH/hexane. The products 3l and 3m were isolated by recrystallizationfrom EtOAc/hexane. 1H NMR spectra were recorded at 400 MHz, and 13C NMR spectra wererecorded at 100 MHz in DMSO-d6 (For 3j, in a mixture of DMSO-d6 and methanol-d4). Elemental analyses were performed at the Microanalytical Center of Kyoto University. The analytical and spectral data of 3a,10 3b-c,11 3d,12 3e,13 3f,14 3g-h,10 and 3j-l,7 are fully consistent with those reported previously. The products 3i,15 and 3m16 were characterized below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With hydrogenchloride; urea In pyridine; water | Part B: The preparation of 6-chloro-2,4-quinazoline-dione. Urea (2.64 g) and 5-chloro-2-amino benzamide (3.75 g) were dissolved in 100 mL of pyridine. To this solution was added 10percent HCl (aq.) (6 drops) and the resulting solution was refluxed for 12-18 hours. The reaction mixture was evaporated to dryness and the resulting residue was suspended in 125 mL of water. The pH of the suspension was adjusted to 6 with dilute hydrochloric acid and the solid was recovered by filtration. The filter cake was washed well with water and was dried to yield 3.27 g of buff powder (76percent): 1 H NMR (DMSO-d6, 300 MHz) δ11.45 (s, 1H), 11.25 (s, 1H), 7.81 (d, 1H), 7.66 (dd, 1H), 7.18 (d, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With triethylamine In tetrahydrofuran at 0 - 20℃; for 3h; | |
94% | With triethylamine In tetrahydrofuran at 0℃; for 3h; | 1.b 2-(2-carbamoyl-4-chlorophenyl) ethyl oxalate (I-3) Dissolve 2-amino-5-chlorobenzamide (I-2, 3.0g, 17.6mmol) and triethylamine (2.9mL, 21.1mmol) in 110mL dry tetrahydrofuran, and dropwise add to the reaction solution with stirring at 0°C Monoethyl oxalyl chloride (2.1mL, 19.4mmol) was added dropwise, and the temperature was raised to room temperature for 3h. The reaction was monitored by TLC. Dilute with 300mL of water to precipitate a white solid. Filter with suction and wash the filter cake with water (10 mL×3). The filter cake was dried to constant weight to obtain 4.46 g of white solid with a yield of 94%. |
With pyridine |
46 2'-Carbamoyl-4'-chlorooxanilic acid ethyl ester. 58 EXAMPLE 46 2'-Carbamoyl-4'-chlorooxanilic acid ethyl ester. 58 2-Amino-5-chlorobenzamide (3.41 g, 0.02 mole) is condensed with 2.46 ml (0.022 mole) of ethyl oxalyl chloride in a manner similar to example 3, giving 4.57 g of the title compound, m.p. 204°-210° C., after crystallization from acetonitrile. Elemental Analysis for C11 H11 ClN2 O4: Calc'd: C, 48.8; H, 4.10; N, 10.33; Cl, 13.10. Found: C, 48.65; H, 3.98; N, 10.26; Cl, 12.84. | ||
29 2'-Carbamoyl-4'-chlorooxanilic acid ethyl ester. 58 EXAMPLE 29 2'-Carbamoyl-4'-chlorooxanilic acid ethyl ester. 58 2-Amino-5-chlorobenzamide (3.41 g., 0.02 mole) is condensed with 2.46 ml. (0.022 mole) of ethyl oxalyl chloride in a manner similar to example 12, giving 4.57 g. of the title compound, m.p. 204°-210° C., after crystallization from acetonitrile. Elemental Analysis for C11 H11 ClN2 O4: Calc'd: C, 48.8; H, 4.10; N, 10.35; Cl, 13.10: Found: C, 48.65; H, 3.98; N, 10.26; Cl, 12.84. | ||
29 2'-Carbamoyl-4'-chlorooxanilic acid ethyl ester. 58 EXAMPLE 29 2'-Carbamoyl-4'-chlorooxanilic acid ethyl ester. 58 2-Amino-5-chlorobenzamide (3.41 g., 0.02 mole) is condensed with 2.46 ml. (0.022 mole) of ethyl oxalyl chloride in a manner similar to example 12, giving 4.57 g. of the title compound, m.p. 204°-210° C., after crystallization from acetonitrile. Elemental Analysis for C11 H11 ClN2 O4: Calc'd: C, 48.8; H, 4.10; N, 10.35; Cl, 13.10. Found: C, 48.65; H, 3.98; N, 10.26; Cl, 12.84. | ||
29 2'-Carbamyl-4'-chlorooxanilic acid ethyl ester. 58 EXAMPLE 29 2'-Carbamyl-4'-chlorooxanilic acid ethyl ester. 58 2-Amino-5-chlorobenzamide (3.41 g., 0.02 mole) is condensed with 2.46 ml. (0.022 mole) of ethyl oxalyl chloride in a manner similar to example 12, giving 4.57 g. of the title compound, m.p. 204°-210° C., after crystallization from acetonitrile. Elemental Analysis for C11 H11 ClN2 O4: Calc'd: C, 48.8; H, 4.10; N, 10.35; Cl, 13.10. Found: C, 48.65; H, 3.98; N, 10.26; Cl, 12.84. | ||
46 2'-Carbamoyl-4'-chlorooxanilic acid ethyl ester. 58 EXAMPLE 46 2'-Carbamoyl-4'-chlorooxanilic acid ethyl ester. 58 2-Amino-5-chlorobenzamide (3.41 g, 0.02 mole) is condensed with 2.46 ml (0.022 mole) of ethyl oxalyl chloride in a manner similar to example 3, giving 4.57 g of the title compound, m.p. 204°-210° C., after crystallization from acetonitrile. Elemental Analysis for C11 H11 CIN2 O4: Calc'd: C, 48.8; H, 4.10; N, 10.35; Cl, 13.10. Found: C, 48.65; H, 3.98; N, 10.26; Cl, 12.84. | ||
46 2'-Carbamoyl-4'-chlorooxanilic acid ethyl ester. 58 EXAMPLE 46 2'-Carbamoyl-4'-chlorooxanilic acid ethyl ester. 58 2-Amino-5-chlorobenzamide (3.41 g, 0.02 mole) is condensed with 2.46 ml (0.022 mole) of ethyl oxalyl chloride in a manner similar to example 3, giving 4.57 g of the title compound, m.p. 204°-210°C., after crystallization from acetonitrile. Elemental Analysis for C11 H11 ClN2 O4: Calc'd: C, 48.8; H, 4.10; N, 10.35; Cl, 13.10. Found: C, 48.65; H, 3.98; N, 10.26; Cl, 12.84. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With ammonia In tetrahydrofuran at 0 - 20℃; | 24 Preparation of phenol 74 5-Chloroisatoic anhydride (76, 50.0 g, 250 mol) was suspended in anhydrous THF (660 mL). The mixture was cooled to 0° C. and dry ammonia was bubbled through the mixture for 2 h. The ice bath was removed, and the mixture warmed to room temperature. Stirring continued overnight at room temperature. The volatiles were removed in vacuo, and the residue was suspended in a 3:1 solution of water to saturated sodium bicarbonate and stirred for 30 min. The white precipitate which formed was filtered. The filtrate was back-extracted with EtOAc (3×200 mL) and the combined extracts were rinsed with brine (1×100 mL) and then dried over Na2SO4. The solution was concentrated. The solids were checked for purity, and when verified that they were of equal purity, combined to afford 77 as a white solid (39 g, 91%). |
88% | With ammonium hydroxide for 4h; Ambient temperature; | |
81% | With ammonia In tetrahydrofuran Ambient temperature; |
With ammonia In water at 20℃; for 1h; | 4.1.5. General procedure for preparation of aminobenzamides 10b,c General procedure: A mixture of 0.01 mol of 2H-3,1-benzoxazine-2,4(1H)-diones 9b,c and 25 ml of aqueous ammonia solution (25%) was stirred for 1 h. The solid precipitate was removed by filtration, washed with an aqueous ammonia solution (5%) and crystallized from ethanol. | |
With ammonium hydroxide for 1h; | 4.1.5. General procedure for preparation of 2-amino-5-chlorobenzamide 2b and 2-amino-5-bromobenzamide 2c [12] General procedure: A mixture of 0.01 mol of 6-R-7-R1-1H-benzo[d] [1,3] oxazine-2,4-diones 8b,c and 25 ml of aqueous ammonia solution (25%) was stirred for 1 h. The solid precipitate was removed by filtration,washed with an aqueous ammonia solution (5%) and crystallized from ethanol | |
With ammonia In water for 1h; | 4 Preparation of 2-amino-5-chlorobenzamide 15b A mixture of 0.01 mol of 6-R-7-R1-1H-benzo[d][1,3]oxazine-2,4-diones 14a and 25 mL of aqueous ammonia solution (25%) was stirred for 1 h. The solid precipitate was removed by filtration, washed with an aqueous ammonia solution (5%) and crystallized from ethanol. | |
With ammonium carbonate In 1,4-dioxane at 60℃; | General Procedure for the Preparation of Anthranilamide(13). General procedure: Compound 13 was prepared according to the procedurepreviously reported.37 A suspension of isatoic anhydride 12 (40mmol), ammonium carbonate (160 mmol), and 1,4-dioxane(150 mL) was heated at 60 °C. After being stirred for 5-8 h,the reaction mixture was cooled to room temperature andevaporated under reduced pressure, and then water (200 mL)was added to the residue, which was extracted three times withEtOAc (300 mL). The organic layer was washed with brine(100 mL), dried over anhydrous Na2SO4, filtered, andconcentrated to afford compound 13 in yields of 80-85%. | |
With ammonium carbonate In 1,4-dioxane at 60℃; for 8h; | Synthesis of Anthranilamides (3) General procedure: A suspension of isatoic anhydride (35 mmol), ammonium carbonate (140 mmol), and 1,4-dioxane (150 mL) was heated at 60 °C. After stirring for 8 h, the reaction mixture was cooled to room temperature and evaporated underreduced pressure, and then water (200 mL) was added to the residue, which was extracted with DCM (80 mL × 3). The organic layerwas dried over anhydrous Na2SO4, and concentrated to give compound 3 in yield of 84%. | |
With ammonium carbonate In 1,4-dioxane at 60℃; for 8h; | Synthesis of substituted Anthranilamides (9). General procedure: A suspension of substituted isatoic anhydride (35 mmol), ammonium carbonate (140 mmol), and 1,4-dioxane (150 mL) was heated at 60 °C. After stirring for 8 h, the reaction mixture was cooled to room temperature and evaporated under reduced pressure, and then water (200 mL) was added to the residue, which was extracted with CH2Cl2 (380 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated to give compounds 9 in yields of 63-94%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: 5-chloro-2-hydroxybenzaldehyde; 2-Amino-5-chlorobenzamide for 0.5h; Reflux; Stage #2: With toluene-4-sulfonic acid for 1h; Reflux; Stage #3: With 2,3-dicyano-5,6-dichloro-p-benzoquinone | 1 ELF-97 A solution of anthranilamide (2.000 g, 11.7 mmol, 1.0 eq.) in dry EtOH (20 mL) is treated with 5-chlorosalicylaldehyde (1.831 g, 11.7 mmol, 1.0 eq.), and the mixture is refluxed for 30 minutes. Then, para-toluenesulfonic acid (PTSA) (40 mg, 0.234 mmol, 0.02 eq.) is added, and refluxing is continued for another hour. The reaction mixture is brought down to room temperature and treated portionwise with 2,3-dichloro-5,6-(dicyano-1,4-benzoquinone (DDQ) (2.678 g, 11.8 mmol, 1.01 eq.). Stirring is continued overniglht. The resulting crude suspension is filtered and the filter cake washed 2 times with EtOH and 2 times with diethyl ether. ELF-97 (3.41 g, 11.11 mmol, 95 %) is obtained as a light beige powder and used without further purification in a later step.1H-NMR (300 MHz, CDCI3): δ (ppm) = 13.38 (s, 1H), 12.64 (s, 1H), 8.29 (s, 1H), 8.10 (s,1H), 7.88 (q, J =7.8 Hz, 2H), 7.49 (d, J = 7.6 Hz,1H), 7.05 (d, J = 8.8 Hz, 1H) |
88% | Stage #1: 5-chloro-2-hydroxybenzaldehyde; 2-Amino-5-chlorobenzamide With toluene-4-sulfonic acid In ethanol for 1h; Reflux; Stage #2: With 2,3-dicyano-5,6-dichloro-p-benzoquinone In ethanol at 0℃; for 1h; | |
86% | Stage #1: 5-chloro-2-hydroxybenzaldehyde; 2-Amino-5-chlorobenzamide With p-toluenesulfonic acid monohydrate In ethanol for 1h; Reflux; Stage #2: With 2,3-dicyano-5,6-dichloro-p-benzoquinone In ethanol; lithium hydroxide monohydrate at 0℃; for 1h; |
86% | Stage #1: 5-chloro-2-hydroxybenzaldehyde; 2-Amino-5-chlorobenzamide With toluene-4-sulfonic acid In ethanol for 1h; Reflux; Stage #2: With 2,3-dicyano-5,6-dichloro-p-benzoquinone In ethanol at 0℃; for 1h; | 2 Preparation of 2-(2'-hydroxy-5'-chlorophenyl)-6-chloro-4(3H)-quinazolinoneIn a 25 ml three-necked flask, a mixture of 4-chloroanthranilamide (0.170 g, 1.0 mmol), 5-chlorosalicydehyde (0.156 g, 1.0 mmol) and TsOH.H2O (18.0 mg, 0.1 mmol) were dissolved in 10 ml of anhydrous ethanol and heated at reflux for 1 hour. The reaction mixture was then cooled to 0° C. and 2,3-dichloro-4,5-dicyano-1,4-benzoquinone (0.228 g, 1.0 mmol) was added. The resultant suspension was stirred at 0° C. for another 1 hour and a greenish precipitate was formed. The solid was collected by filtration and washed with a small amount of cooled ethanol to afford 0.301 g of the desired greenish-white compound. Yield: 86.0%. 1H NMR (300 MHz, DMSO-d6), δ8.29 (d, J=2.2 Hz, 1H), δ8.10 (d, J=2.1 Hz, 1H), δ7.83-7.92 (m, 2H), δ7.49 (dd, J=2.5, 8.9 Hz, 1H), δ7.05 (d, J=8.8 Hz, 1H) 13C NMR (75 MHz, DMSO-d6) δ (ppm): 135.7, 134.0, 132.0, 129.9, 129.3, 127.8, 125.8, 123.0, 121.8, 120.0, 116.3. |
86% | Stage #1: 5-chloro-2-hydroxybenzaldehyde; 2-Amino-5-chlorobenzamide With toluene-4-sulfonic acid In ethanol at 90℃; for 1h; Stage #2: With 2,3-dicyano-5,6-dichloro-p-benzoquinone In ethanol at 90℃; for 1h; | |
83% | Stage #1: 5-chloro-2-hydroxybenzaldehyde; 2-Amino-5-chlorobenzamide With toluene-4-sulfonic acid In ethanol; lithium hydroxide monohydrate for 1h; Reflux; Stage #2: With 2,3-dicyano-5,6-dichloro-p-benzoquinone In ethanol; lithium hydroxide monohydrate at 5℃; for 1h; | 24 Preparation of phenol 74 5-Chloroanthranilamide (77, 670 mg, 3.9 mmol) and 5-chlorosalicylaldehyde (78, 620 mg, 4.0 mmol) were added to EtOH (10 mL). p-Toluenesulfonic acid monohydrate (20 mg, 0.11 mmol) was added to the reaction mixture and the solution was refluxed 1 h. The reaction solution was cooled to 5° C. and added 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ, 0.90 g, 4.0 mmol). The solution was stirred for 1 h at 5° C. A white precipitate formed, and was subsequently filtered. The precipitate was rinsed with cold EtOH (3×10 mL). Phenol 74 was obtained as a white solid (1.0 g, 83%). |
With toluene-4-sulfonic acid; 2,3-dicyano-5,6-dichloro-p-benzoquinone 1.) EtOH, reflux, 30 min, 2.) reflux, 1 h, 3.) room temperature, 2 h; Yield given. Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen In ethanol | ||
With hydrogenchloride; tin(ll) chloride In water | ||
With hydrogen In ethanol at 120℃; for 5h; Autoclave; | General procedure: The chemoselective hydrogenation of nitro aromatics with H2 as the hydrogen donor was carried out in a 100 mL stainless-steel autoclave with an external stirring and temperature controller. In a typical experiment, 10 mmol of nitro aromatics, 100 mg of catalysts and 10 mL of ethanol were introduced into the autoclave. Before starting the reaction, the autoclave was purged three times with 5 bar of hydrogen to remove the air, and pressurized to 2 MPa H2, followed by heating to 120 °C. The stirring speed is kept at 800 rpm. After a period of reaction, the autoclave was cooled down to room temperature and the remaining H2 was carefully released. The liquid solution was separated from the reaction mixture by filtration for further analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With toluene-4-sulfonic acid In methanol at 0 - 20℃; for 2h; | |
With hydrogenchloride; sodium nitrite | ||
With hydrogenchloride; sodium nitrite In water; N,N-dimethyl-formamide at 0℃; for 1.66667h; | General Procedure for the Preparation of 1,2,3-Benzotriazin-4-ones (14). General procedure: Compound 14 was prepared according tothe procedure previously reported.38 A solution of sodiumnitrite (4.14 g, 60 mmol) in 0.5 N HCl (240 mL) was stirred at0 °C for 20 min. Anthranilamide 13 (30 mmol) dissolved inN,N-dimethylformamide (DMF, 15 mL) was then addeddropwise to the solution described above for 40 min. Afterthe mixture had been stirred for an additional 1 h at 0 °C, 30%aqueous ammonia was added slowly to adjust the pH to 10.0.The reaction mixture was allowed to stir for 15 min and thenreacidified to pH 2.0. After the mixture had been stirred for 30min, the precipitated product was filtered off with suction,washed with water (200 mL), and dried to afford compound 14in yields of 75-83%. |
Stage #1: 2-Amino-5-chlorobenzamide With hydrogenchloride at 0℃; for 0.333333h; Stage #2: With sodium nitrite In water at 0℃; for 2.66h; Stage #3: With sodium hydroxide In water for 0.25h; | Synthesis of 1,2,3-Benzotriazin-4-ones (4) General procedure: A solution of anthranilamide (30 mmol) in 1 N HCl (120 mL) was stirred at 0 °C for 20 min. Then, sodium nitrite (60 mmol) dissolved in deionized water (100 mL) was added dropwise to the above solution for 40 min. After another 2 h of stirring at 0 °C, 30% NaOH solution was added slowly to adjust the pH to 8.0. The reaction mixture was allowed to stir vigorously for 15 min. The precipitated product was filtered off with suction, washed with deionized water (200 mL), and dried to afford compound 4 in yield of 82%. | |
Stage #1: 2-Amino-5-chlorobenzamide With hydrogenchloride In water at 0℃; for 0.333333h; Stage #2: With sodium nitrite In water at 0℃; for 2.66667h; Stage #3: With sodium hydroxide In water for 0.25h; | Synthesis of substituted 1,2,3-benzotriazin-4-ones (10)(except 8-nitrobenzo[d][1-3]triazin-4(3H)-one). General procedure: A solution of anthranilamide (30 mmol) in 1N HCl (120 mL) was stirred at 0 °C for 20 min. Then, sodium nitrite (60 mmol) dissolved in deionized water (100 mL) was added dropwise to the above solution for 40 min. After another 2 h of stirringat 0 °C, 30% NaOH solution was added slowly to adjustp H value to 8.0. The reaction mixture was allowed to stir vigorously for 15 min. The precipitated product was filtered, washed with deionized water (200 mL), and dried to afford compounds 10 in yields of 40-92%. | |
With hydrogenchloride; sodium nitrite In N,N-dimethyl-formamide at 0℃; for 0.666667h; | Synthesis of 1,2,3-benzotriazin-4-one (2) General procedure: A solution of sodium nitrite (4.14 g, 60 mmol) in 0.5 N HCl (240 mL) was stirred at 0 °C for 20 min. Then anthranilamide (3.96 g, 30 mmol) dissolved in N, N-dimethylformamide (DMF, 15 mL) was added dropwise to the above solution for 40 min. After another 1 h of stirring at 0 °C, 30% aqueous ammonia was added slowly to adjust the pH to 10.0. The reaction mixture was allowed to stir vigorously for 15 min and then add acid to adjust pH 2.0. After stirring for 30 min, the precipitated product was filtered off with suction, washed with water (200 mL) and dried to afford afford the product. The yields of substituted 1,2,3-benzotriazin-4-ones in yields of 84-92%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | 2-Amino-5-chlorobenzoic acid (1-1, 5.0 g, 29.1 mmol) was dissolved in 50 mL of dry tetrahydrofuran, and triphosgene (2.9 g, 9.9 mmol) was added with stirring, and the temperature was raised to 65 C. for 16 h. TLC monitored the reaction to completion. The temperature was reduced to room temperature, the solvent was distilled off under reduced pressure, 1N ammonia water (233 mL) was added, the temperature was raised to 65C for 1 hour, and the temperature was reduced to 0C to precipitate a white solid. The reaction was completed by TLC. Reduce to room temperature, filter with suction and wash the filter cake with water (10mL×3). The filter cake is dried to constant weight to obtain 4.23g of white powdery solid with a yield of 85%. | |
With ammonium chloride; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 20℃; for 15h; | General procedure: The syntheses of compounds 3a-3x were mainly referred to literature method [35]. A mixture of 1a-1q, 1w, 1x (2mmol), EDC?HCl (575mg, 3mmol), HOBt (446mg, 3.3mmol), NH4Cl (348mg, 6.5mmol) and DIPEA (2.3mL, 13mmol) in DMSO (7mL) was stirred at room temperature for 15h. The mixture was extracted with EtOAc three times, and the combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford 3a-3q, 3w, 3x. A mixture of 2r-2v (2mmol) and NH3·H2O (25-28wt%, 80mmol) in sealed tube was heated at 100C for 12h. The mixture was cooled to room temperature and extracted with EtOAc three times. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford 3r-3v. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | Stage #1: Ethyl oxalyl chloride; 2-Amino-5-chlorobenzamide With pyridine at 20℃; for 18h; Stage #2: With acetic anhydride; acetic acid for 16h; Reflux; | |
Stage #1: Ethyl oxalyl chloride; 2-Amino-5-chlorobenzamide With pyridine at 20℃; for 18h; Stage #2: With acetic anhydride In acetic acid for 16h; Heating / reflux; | 348 Ethyl chlorooxoacetate (2.0 mL) was added to a solution of 2-amino-5-chlorobenzamide (2.50 g) in pyridine (15 mL), and the mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated under reduced pressure, and the resultant residue was dissolved in acetic acid (50 mL). Acetic anhydride (5.0 mL) was added to the solution, and the mixture was heated under reflux for 16 hours. The solvent was distilled away under reduced pressure, and ethanol was added to the residue. Crystals precipitated were collected by filtration and washed, to thereby give the title compound (2.71 g).1H-NMR(DMSO-d6) δ:1.35(3H,t,J=7.1Hz), 4.38[2H,q,J=7.1Hz), 7.85(1H,d,J=8.6Hz), 7.91(1H,dd,J=8.6,2.3Hz), 8.10(1H,d,J=2.3Hz), 12.85(1H,br.s). MS(ESI)m/z:253(M+H)+. | |
With acetic anhydride In pyridine; ethanol; acetic acid | R.348 Ethyl 6-chloro-4-oxo-1,4-dihydroquinazoline-2-carboxylate: REFERENTIAL EXAMPLE 348 Ethyl 6-chloro-4-oxo-1,4-dihydroquinazoline-2-carboxylate: Ethyl chlorooxoacetate (2.0 ml) was added to a solution of 2-amino-5-chlorobenzamide (2.50 g) in pyridine (15 ml), and the mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated under reduced pressure, and the resultant residue was dissolved in acetic acid (50 ml). Acetic anhydride (5.0 ml) was added to the solution, and the mixture was heated under reflux for 16 hours. The solvent was distilled off under reduced pressure, and ethanol was added to the residue. Crystals deposited were collected by filtration and washed to obtain the title compound (2.71 g). 1H-NMR (DMSO-d6) δ: 1.35(3H,t,J=7.1 Hz), 4.38(2H,q,J=7.1 Hz), 7.85(1H,d,J=8.6 Hz), 7.91(1H,dd,J=8.6, 2.3 Hz), 8.10(1H,d,J=2.3 Hz), 12.85(1H,br.s). MS (ESI) m/z: 253(M+H)+. |
Stage #1: Ethyl oxalyl chloride; 2-Amino-5-chlorobenzamide With pyridine at 20℃; for 18h; Stage #2: With acetic anhydride In acetic acid for 16h; Heating / reflux; | 348 ethyl 6-chloro-4-oxo-1,4-dihydroquinazoline-2-carboxylate: [Referential Example 348] ethyl 6-chloro-4-oxo-1,4-dihydroquinazoline-2-carboxylate: ethyl chlorooxoacetate (2.0 ml) was added to a solution of 2-amino-5-chlorobenzamide (2.50 g) in pyridine (15 ml), and the mixture was stirred at room temperature for 18 hours.. The reaction mixture was concentrated under reduced pressure, and the resultant residue was dissolved in acetic acid (50 ml).. acetic anhydride (5.0 ml) was added to the solution, and the mixture was heated under reflux for 16 hours.. The solvent was distilled off under reduced pressure, and ethanol was added to the residue.. Crystals deposited were collected by filtration and washed to obtain the title compound (2.71 g).1H-NMR (DMSO-d6) δ: 1.35(3H,t,J=7.1Hz), 4.38(2H,q,J=7.1Hz), 7.85(1H,d,J=8.6Hz), 7.91(1H,dd,J=8.6,2.3Hz), 8.10(1H,d,J=2.3Hz), 12.85(1H,br.s). MS (ESI) m/z: 253(M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; toluene; | EXAMPLE 15 6-Chloro-(1h,3h)-Quinazolin-2,4-Dione To a solution of 5-chloroanthranilamide (3.4 g) in tetrahydrofuran (50 ml) is added phosgene (16 ml, 1.93M solution in toluene) via an addition funnel. The reaction mixture is stirred at room temperature for 4 hours and then heated to reflux for another two hours. The reaction mixture is concentrated to a total volume about 10 ml. After cooling, the title compound (3.72 g) having the following physical data is collected by filtration and dried in vacuum. | |
In tetrahydrofuran; toluene; | Reference Example 11 6-chloro-(1H,3H)-quinazolin-2,4-dione STR78 To a solution of 5-chloroanthranilamide (3.4 g)in tetrahydrofuran (50 mL) was added phosgene (16 mL, 1.93M solution in toluene) via an addition funnel. The reaction mixture was stirred at room temperature for 4 hours and then heated to reflux for another two hours. The reaction mixture was concentrated to a total volume about 10 mL. After cooling, the title compound (3.72 g) having the following physical data, was collected by filtration and dried in vacuum. NMR (200 MHz, DMSO-d6): delta 7.19 (d, 1H), 7.69 (dd, 1H), 7.82 (d, 1H), 11.28 (broad, 1H), 11.45 (broad, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With hydrogenchloride; urea; In pyridine; water; | Part B: The preparation of 6-chloro-2,4-quinazoline-dione. Urea (2.64 g) and 5-chloro-2-amino benzamide (3.75 g) were dissolved in 100 mL of pyridine. To this solution was added 10% HCl (aq.) (6 drops) and the resulting solution was refluxed for 12-18 hours. The reaction mixture was evaporated to dryness and the resulting residue was suspended in 125 mL of water. The pH of the suspension was adjusted to 6 with dilute hydrochloric acid and the solid was recovered by filtration. The filter cake was washed well with water and was dried to yield 3.27 g of buff powder (76%): 1 H NMR (DMSO-d6, 300 MHz) delta11.45 (s, 1H), 11.25 (s, 1H), 7.81 (d, 1H), 7.66 (dd, 1H), 7.18 (d, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With silica-gel-supported sulfuric acid In toluene for 2.5h; Inert atmosphere; Reflux; | |
89% | With water; potassium carbonate In water at 150℃; for 0.5h; Microwave irradiation; | Microwave-assisted catalytic hydration of organonitriles to benzamides starting materials: general procedure C General procedure: Adapted from a literature procedure,1 the appropriate organonitrile (1.0 eq.) and K2CO3(0.2eq.)wereaddedtoamicrowavetubewithastir-barwithdeionizedwater(8.5mLpermmolsubstrate).Afterirradiationundermicrowaveat150°Cfor30minutes,thereactionmixturewascooled,extractedwithEtOAc(320mL),thecombinedphasesdriedoverMgSO4andexcesssolventremovedinvacuo.TheresiduewaspurifiedbyFCC,ifrequired,togivethetitlecompound. |
With potassium hydroxide; ethanol Heating / reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With indium(III) bromide In acetonitrile at 20℃; for 1h; | 1.2 General Procedure for Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones (3a-3aa) General procedure: Indiumtribromide (0.5 mol %) was added to a solution of 2-amino benzanilide or 2-amino-5-chloro benzamide (1 mmol) and desired aldehydes (1 mmol) in acetonitrile (3mL). The mixture was stirred at room temperature for the specified period of time. The progress of the reaction was monitored by TLC. After completion of reaction, solvent was evaporated at reduced pressure, and solid was partitioned between ethyl acetate (15.0 mL) and water (15.0mL), and transferred to a separatory funnel. The organic layer was washed with water, and brine, dried over anhydrous Na2SO4 (s) and concentrated in vacuo. The residue was purified by recrystallization from CH2Cl2/Hexane to afford the corresponding pure 2,3-dihydroquinazolin-4(1H)-ones (3a-3aa) as solids with excellent yields. |
82% | In ethanol at 70℃; for 0.833333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With indium(III) bromide In acetonitrile at 20℃; for 1h; | 1.2 General Procedure for Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones (3a-3aa) General procedure: Indiumtribromide (0.5 mol %) was added to a solution of 2-amino benzanilide or 2-amino-5-chloro benzamide (1 mmol) and desired aldehydes (1 mmol) in acetonitrile (3mL). The mixture was stirred at room temperature for the specified period of time. The progress of the reaction was monitored by TLC. After completion of reaction, solvent was evaporated at reduced pressure, and solid was partitioned between ethyl acetate (15.0 mL) and water (15.0mL), and transferred to a separatory funnel. The organic layer was washed with water, and brine, dried over anhydrous Na2SO4 (s) and concentrated in vacuo. The residue was purified by recrystallization from CH2Cl2/Hexane to afford the corresponding pure 2,3-dihydroquinazolin-4(1H)-ones (3a-3aa) as solids with excellent yields. |
87% | With Sodium borate In water at 60℃; for 3h; | General procedure for the synthesis of 2,3-dihydroquinazolinones/3,4-dihydrobenzothiadiazine 1,1-dioxide/benzothiazoles General procedure: 2-Aminobenzamide/2-aminobenzenesulfonamide/2-aminothiophenol (0.3mmol), aldehyde (0.3mmol), and borax (20mol %) were taken in a 50ml round bottom flask, and the reaction mixture was stirred in H2O (2ml) at 60 for a period of time till the completion of the reaction (monitored by TLC). After completion of the reaction, it was extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography to give the desired product. All compounds were well characterized by FT-IR, 1H, 13C NMR, and melting point analysis. |
83% | In ethanol at 70℃; for 0.75h; |
at 90℃; for 2h; | ||
In water for 2h; Reflux; | 25 6-chloro-2-phenylquinazolin-4(3Η)-one 2-Amino-5-chlorobenzamide(171 mg, lmmol), Benzaldehyde (106 mg, lmmol), Water (1 · OmL)And then added to 5mL single-mouth bottle. The mixture was reacted at reflux temperature for 2 hours and then cooled to room temperature. Then join[Cp * Ir (H20) 3] [0Tf] 2 (6.8 mg, 0. ol mmol, 1 mol%) was reacted at reflux temperature for 1 hour and then cooled to room temperatureTheThe solvent was removed under vacuum under reduced pressure and then passed through a column chromatography (developing solvent): Ethyl acetate / n-hexane) to give the pure title compoundObjects,Yield: 84%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With indium(III) bromide In acetonitrile at 20℃; for 0.166667h; | 1.2 General Procedure for Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones (3a-3aa) General procedure: Indiumtribromide (0.5 mol %) was added to a solution of 2-amino benzanilide or 2-amino-5-chloro benzamide (1 mmol) and desired aldehydes (1 mmol) in acetonitrile (3mL). The mixture was stirred at room temperature for the specified period of time. The progress of the reaction was monitored by TLC. After completion of reaction, solvent was evaporated at reduced pressure, and solid was partitioned between ethyl acetate (15.0 mL) and water (15.0mL), and transferred to a separatory funnel. The organic layer was washed with water, and brine, dried over anhydrous Na2SO4 (s) and concentrated in vacuo. The residue was purified by recrystallization from CH2Cl2/Hexane to afford the corresponding pure 2,3-dihydroquinazolin-4(1H)-ones (3a-3aa) as solids with excellent yields. |
96% | With phosphotungstic acid In water at 20℃; for 0.1h; | |
89% | With N-ocetylpyridinium 3-sulfuric acid salt In ethanol at 35℃; for 0.0833333h; | 2.6 A Typical Procedure fortheSynthesis of2-(4-methoxyphenyl) -2,3-dihydroquinazoline-4(1H) -one (12d) General procedure: A mixture of 2-amino-benzamide (1mmol), 4-methoxy-benzaldehyde(1mmol) and catalyst (0.05mol%) in ethanol wasstirred at 35°C for 5min. After cooling the reaction mixtureto ambient temperature, the residue was filtered and washedwith ethanol (98% yield). |
84% | In ethanol at 70℃; for 0.666667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With C72H61O4P In toluene at -45℃; for 24h; Inert atmosphere; Molecular sieve; optical yield given as %ee; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With potassium carbonate In 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone at 150℃; for 0.166667h; Microwave irradiation; | 1.10 2-Amino-5-chlorobenzamide (500 mg, 2.93 mmol), diphenylcarbonate (628 mg, 2.93 mmol) and K2CO3 (608 mg, 4.40 mmol) were suspended in DMPU (3 mL) and the mixture heated to 150° C. for 10 min under microwave irradiation. After cooling to ambient temperature, the suspension was poured into water, forming a precipitate. The mixture was filtered, and washed with EtOAc. The precipitate was heated in boiling EtOAc, filtered, and washed with cold EtOAc to give the title compound as an orange powder (594 mg, 86%).1H NMR (DMSO): 9.62 (1H, br s), 7.57 (1H, d, J 2.6), 7.22 (1H, dd, J 8.8 and 2.6) and 6.85 (1H, d, J 8.7). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With indium(III) bromide In acetonitrile at 20℃; for 0.5h; | 1.2 General Procedure for Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones (3a-3aa) General procedure: Indiumtribromide (0.5 mol %) was added to a solution of 2-amino benzanilide or 2-amino-5-chloro benzamide (1 mmol) and desired aldehydes (1 mmol) in acetonitrile (3mL). The mixture was stirred at room temperature for the specified period of time. The progress of the reaction was monitored by TLC. After completion of reaction, solvent was evaporated at reduced pressure, and solid was partitioned between ethyl acetate (15.0 mL) and water (15.0mL), and transferred to a separatory funnel. The organic layer was washed with water, and brine, dried over anhydrous Na2SO4 (s) and concentrated in vacuo. The residue was purified by recrystallization from CH2Cl2/Hexane to afford the corresponding pure 2,3-dihydroquinazolin-4(1H)-ones (3a-3aa) as solids with excellent yields. |
94% | With phosphotungstic acid In water at 20℃; for 0.133333h; | |
82% | With aluminum oxide; citric acid at 20℃; for 0.166667h; neat (no solvent); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium hydroxide In toluene at 90℃; for 20h; | Typical procedure of synthesis of 4(3H)-quinazolinones General procedure: To an oven-dried 20 cm3 test tube with a ground-in stopperequipped with a stir bar were added anthranilamide (1.0 mmol), benzyl alcohol (1.0 mmol), KOH (2.0 mmol),and 4 cm3 toluene. The test tube was put in an oil bath potpreheated at 90 C and the mixture was stirred for 20 h at90 C. After cooling to room temperature, the reactionmixture was added about 5 g silica gel and directly condensedon a rotator under vacuum. The resulting residualwas transferred to a silica gel chromatography column andeluted with a solution of petroleum ether and ethyl acetate[4/1 (v/v)] to give a white solid 2-phenyl-4(3H)-quinazolinone.For some products (3f, 3g, 3n, and 3t) onlysparingly soluble in ethyl acetate, the reaction mixtureswere condensed in vacuo on a rotary evaporator. Theresiduals were washed three times with water and oncewith ethyl acetate, and then dried in an infrared oven togive the desired products pure enough for NMR analysis. |
86% | With iron (ΙΙΙ) nitrate nonahydrate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; oxygen; potassium hydroxide In toluene at 100℃; for 12h; | |
84% | With bis[dichlorido(η5-1,2,3,4,5-pentamethyl-cyclopentadienyl)iridium(III)] In 5,5-dimethyl-1,3-cyclohexadiene for 48h; Inert atmosphere; Reflux; |
83% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tetra-n-butylammonium hexafluoridophosphate In lithium hydroxide monohydrate; acetonitrile at 20℃; for 3h; Electrochemical reaction; | |
81% | With iodine; sodium hydroxide In lithium hydroxide monohydrate at 20℃; for 6h; Electrochemical reaction; Green chemistry; | |
80% | With potassium-t-butoxide In neat (no solvent) at 140℃; for 24h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With 2,6-bis[(3aR,8aS)-3a,8a-dihydro-8H-indeno[1,2-d]oxazolin-2-yl]pyridine; scandium tris(trifluoromethanesulfonate) In dichloromethane Molecular sieve; optical yield given as %ee; enantioselective reaction; | |
95% | With 2,6-bis[(3aR,8aS)-3a,8a-dihydro-8H-indeno[1,2-d]oxazolin-2-yl]pyridine; scandium tris(trifluoromethanesulfonate) In dichloromethane at 20℃; Molecular sieve; enantioselective reaction; | General procedure for the enantioselective synthesis of 2-alkyl and 2-aryl-2,3-dihydroquinazolinones General procedure: In an oven dried flask pybox ligand 10 (7.5 μmol) and Sc(OTf)3 (3 μmol) were taken in 1 mL of anhydrous dichloromethane. 50mg of 4Å molecular sieves was added to the solution and the resulting mixture was stirred further. After 3 h, Anthranilamide (1a) (300 μmol) solubilized in 1 mL of dichloromethane was added at the indicated temperature, followed by aldehyde (360 μmol) and stirred until the reaction was completed. Completion of the reaction was ascertained by TLC, and the product was purified by using a small pad of silica gel 60-100 mesh with an eluent of (PEEA, 1:1) to afford dihydroquinazolinones as colourless solids. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With indium(III) bromide In acetonitrile at 20℃; for 0.833333h; | 1.2 General Procedure for Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones (3a-3aa) General procedure: Indiumtribromide (0.5 mol %) was added to a solution of 2-amino benzanilide or 2-amino-5-chloro benzamide (1 mmol) and desired aldehydes (1 mmol) in acetonitrile (3mL). The mixture was stirred at room temperature for the specified period of time. The progress of the reaction was monitored by TLC. After completion of reaction, solvent was evaporated at reduced pressure, and solid was partitioned between ethyl acetate (15.0 mL) and water (15.0mL), and transferred to a separatory funnel. The organic layer was washed with water, and brine, dried over anhydrous Na2SO4 (s) and concentrated in vacuo. The residue was purified by recrystallization from CH2Cl2/Hexane to afford the corresponding pure 2,3-dihydroquinazolin-4(1H)-ones (3a-3aa) as solids with excellent yields. |
80% | With aluminum oxide; citric acid at 20℃; for 0.166667h; neat (no solvent); | |
72% | With carbon nanodots In water; acetonitrile at 40℃; for 0.833333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With iodine In toluene at 110℃; | General procedure for the synthesis of 6 General procedure: A dry 50 mL flask was charged with 2-aminobenzamide 1 (1.1 mmol), 5,5-dimethyl-1,3-cyclohexanedione 2 (1.0 mmol), iodine (0.026 g, 0.01 mmol) and toluene (10.0 mL). The mixture was stirred at 80 C until the reactant 1 was consumed. Then, another equivalent of 2-aminobenzamide was added to the mixture, and refluxed for a few hours. After the completion of the reaction monitored by TLC, toluene was recovered by distillation under reduced pressure, and the residue was purified by silica column chromatography using ethyl acetate and petroleum ether (1:2) as the eluent to give products 6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With iodine In toluene at 110℃; | General procedure for the synthesis of 6 General procedure: A dry 50 mL flask was charged with 2-aminobenzamide 1 (1.1 mmol), 5,5-dimethyl-1,3-cyclohexanedione 2 (1.0 mmol), iodine (0.026 g, 0.01 mmol) and toluene (10.0 mL). The mixture was stirred at 80 C until the reactant 1 was consumed. Then, another equivalent of 2-aminobenzamide was added to the mixture, and refluxed for a few hours. After the completion of the reaction monitored by TLC, toluene was recovered by distillation under reduced pressure, and the residue was purified by silica column chromatography using ethyl acetate and petroleum ether (1:2) as the eluent to give products 6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With iodine In toluene at 50℃; for 10h; | General procedure for the synthesis of 4 General procedure: A dry 50 mL flask was charged with 2-aminobenzamides 1 (2.1 mmol), 5,5-dimethyl-1,3-cyclohexanedione 2 (0.280 g, 2.0 mmol), iodine (0.026 g, 0.01 mmol) and toluene (10.0 mL). The mixture was stirred at 50 C until the reactant 1 was consumed. After the completion of the reaction monitored by TLC, toluene was recovered by distillation under reduced pressure, and the residue was purified by recrystallization in EtOH to give products 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With iodine In toluene at 110℃; for 16h; | General procedure for the synthesis of 3 General procedure: A dry 50 mL flask was charged with 2-aminobenzamides 1 (2.1 mmol), 5,5-dimethyl-1,3-cyclohexanedione 2 (1.0 mmol), iodine (0.026 g, 0.01 mmol) and toluene (10.0 mL). The mixture was stirred at reflux until the reactant 1 was consumed. After the completion of the reaction monitored by TLC, toluene was recovered by distillation under reduced pressure, and the residue was purified by silica column chromatography using ethyl acetate and petroleum ether (1:3) as the eluent to give products 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With pyridine at 0 - 5℃; for 24.5h; | 4.1.7. General procedure for preparation of 5-R-4-R1-2-cinnamamidobenzamides 4a-e, 4f [4,5], 4g-k, 5-R-4-R1-2-(3-phenylpropiolamido)benzamide 4l [8], 4m-q and 5-R-4-R1-2-(3-phenylpropanamido)benzamide 4r [9] 4s-w General procedure: To a cold (0-5 °C) stirred suspension of aminobenzamides 2a-g (0.016 mol) in pyridine (13 ml), 0.016 mol of the appropriate cinnamoyl chloride 3a-e, 3-phenylpropioloyl chloride 3f-k and 3-phenylpropanoyl chloride 3l-o was added over 30 min. After addition was complete, the solution was stirred for 24 h and then poured onto crushed ice. The precipitate was removed by filtration, washed with water, and crystallized from the appropriate solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With diphenyl-phosphinic acid; oxygen; copper(l) chloride In chlorobenzene at 130℃; for 8h; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With diphenyl-phosphinic acid; oxygen; copper(l) chloride In chlorobenzene at 130℃; for 8h; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With diphenyl-phosphinic acid; oxygen; copper(l) chloride In chlorobenzene at 130℃; for 8h; Schlenk technique; | |
67% | With ammonium iodide; ammonium tetrafluroborate; oxalic acid In N,N-dimethyl-formamide at 100℃; Electrolysis; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.6% | In ethanol; for 16h;Reflux; | General procedure: To a refluxing solution of corresponding anthranilamide (1 mmol) in ethanol (30 mL) was added formamidine acetate (2 mmol). The solution was refluxed for about 6 h (monitored by TLC & LCMS for completion), and solvent evaporated under reduced pressure. The residue was further diluted with water (30 mL) and ethyl acetate (50 mL) and the layers separated. The organic layer was dried over anhydrous sodium sulphate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography using hexane: ethyl acetate as eluent to give the corresponding quinazolin-4(3H)-one (4a-b) in good yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With ytterbium(III) triflate; In 1,3,5-trimethyl-benzene; at 165℃; for 6h;Inert atmosphere; | General procedure: A mixture of 2-aminobenzamide (1, 4.0 mmol), carboxamide (2, 6.0 mmol), Yb(OTf)3 (0.20 mmol,5.0 mol%), and mesitylene (5.0 mL) was placed in a 20-mL Pyrex flask equipped with a magnetic stirring bar and a reflux condenser under a flow of argon. The reaction was carried out at 120-165 oC (bath temp.) for 6 h with stirring. Then, the reaction mixture was cooled to room temperature, and analyzed by GLC, GC-MS (EI), and LC-MS (ESI). After evaporation of mesitylene under vacuum,the products (3) were isolated by recrystallization from MeOH/hexane and/or medium pressure column chromatography on silica gel (eluent: EtOAc/hexane = 50/50 ~ EtOAc 100%. For 3j, eluent:MeOH/CHCl3 = 50/50). 1H NMR spectra were recorded at 400 MHz, and 13C NMR spectra wererecorded at 100 MHz in DMSO-d6. The analytical and spectral data of 3a-e,38 3f,39 3g,40 3h,41 and3j,42 were consistent with those reported previously. The product, 3i, was characterized below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With indium(III) bromide In acetonitrile at 20℃; for 0.833333h; | 1.2 General Procedure for Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones (3a-3aa) General procedure: Indiumtribromide (0.5 mol %) was added to a solution of 2-amino benzanilide or 2-amino-5-chloro benzamide (1 mmol) and desired aldehydes (1 mmol) in acetonitrile (3mL). The mixture was stirred at room temperature for the specified period of time. The progress of the reaction was monitored by TLC. After completion of reaction, solvent was evaporated at reduced pressure, and solid was partitioned between ethyl acetate (15.0 mL) and water (15.0mL), and transferred to a separatory funnel. The organic layer was washed with water, and brine, dried over anhydrous Na2SO4 (s) and concentrated in vacuo. The residue was purified by recrystallization from CH2Cl2/Hexane to afford the corresponding pure 2,3-dihydroquinazolin-4(1H)-ones (3a-3aa) as solids with excellent yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With indium(III) bromide In acetonitrile at 20℃; for 1h; | 1.2 General Procedure for Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones (3a-3aa) General procedure: Indiumtribromide (0.5 mol %) was added to a solution of 2-amino benzanilide or 2-amino-5-chloro benzamide (1 mmol) and desired aldehydes (1 mmol) in acetonitrile (3mL). The mixture was stirred at room temperature for the specified period of time. The progress of the reaction was monitored by TLC. After completion of reaction, solvent was evaporated at reduced pressure, and solid was partitioned between ethyl acetate (15.0 mL) and water (15.0mL), and transferred to a separatory funnel. The organic layer was washed with water, and brine, dried over anhydrous Na2SO4 (s) and concentrated in vacuo. The residue was purified by recrystallization from CH2Cl2/Hexane to afford the corresponding pure 2,3-dihydroquinazolin-4(1H)-ones (3a-3aa) as solids with excellent yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With indium(III) bromide In acetonitrile at 20℃; for 0.666667h; | 1.2 General Procedure for Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones (3a-3aa) General procedure: Indiumtribromide (0.5 mol %) was added to a solution of 2-amino benzanilide or 2-amino-5-chloro benzamide (1 mmol) and desired aldehydes (1 mmol) in acetonitrile (3mL). The mixture was stirred at room temperature for the specified period of time. The progress of the reaction was monitored by TLC. After completion of reaction, solvent was evaporated at reduced pressure, and solid was partitioned between ethyl acetate (15.0 mL) and water (15.0mL), and transferred to a separatory funnel. The organic layer was washed with water, and brine, dried over anhydrous Na2SO4 (s) and concentrated in vacuo. The residue was purified by recrystallization from CH2Cl2/Hexane to afford the corresponding pure 2,3-dihydroquinazolin-4(1H)-ones (3a-3aa) as solids with excellent yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With indium(III) bromide In acetonitrile at 20℃; for 1h; | 1.2 General Procedure for Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones (3a-3aa) General procedure: Indiumtribromide (0.5 mol %) was added to a solution of 2-amino benzanilide or 2-amino-5-chloro benzamide (1 mmol) and desired aldehydes (1 mmol) in acetonitrile (3mL). The mixture was stirred at room temperature for the specified period of time. The progress of the reaction was monitored by TLC. After completion of reaction, solvent was evaporated at reduced pressure, and solid was partitioned between ethyl acetate (15.0 mL) and water (15.0mL), and transferred to a separatory funnel. The organic layer was washed with water, and brine, dried over anhydrous Na2SO4 (s) and concentrated in vacuo. The residue was purified by recrystallization from CH2Cl2/Hexane to afford the corresponding pure 2,3-dihydroquinazolin-4(1H)-ones (3a-3aa) as solids with excellent yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With indium(III) bromide In acetonitrile at 20℃; for 1h; | 1.2 General Procedure for Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones (3a-3aa) General procedure: Indiumtribromide (0.5 mol %) was added to a solution of 2-amino benzanilide or 2-amino-5-chloro benzamide (1 mmol) and desired aldehydes (1 mmol) in acetonitrile (3mL). The mixture was stirred at room temperature for the specified period of time. The progress of the reaction was monitored by TLC. After completion of reaction, solvent was evaporated at reduced pressure, and solid was partitioned between ethyl acetate (15.0 mL) and water (15.0mL), and transferred to a separatory funnel. The organic layer was washed with water, and brine, dried over anhydrous Na2SO4 (s) and concentrated in vacuo. The residue was purified by recrystallization from CH2Cl2/Hexane to afford the corresponding pure 2,3-dihydroquinazolin-4(1H)-ones (3a-3aa) as solids with excellent yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With indium(III) bromide In acetonitrile at 20℃; for 0.666667h; | 1.2 General Procedure for Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones (3a-3aa) General procedure: Indiumtribromide (0.5 mol %) was added to a solution of 2-amino benzanilide or 2-amino-5-chloro benzamide (1 mmol) and desired aldehydes (1 mmol) in acetonitrile (3mL). The mixture was stirred at room temperature for the specified period of time. The progress of the reaction was monitored by TLC. After completion of reaction, solvent was evaporated at reduced pressure, and solid was partitioned between ethyl acetate (15.0 mL) and water (15.0mL), and transferred to a separatory funnel. The organic layer was washed with water, and brine, dried over anhydrous Na2SO4 (s) and concentrated in vacuo. The residue was purified by recrystallization from CH2Cl2/Hexane to afford the corresponding pure 2,3-dihydroquinazolin-4(1H)-ones (3a-3aa) as solids with excellent yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With indium(III) bromide In acetonitrile at 20℃; for 0.333333h; | 1.2 General Procedure for Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones (3a-3aa) General procedure: Indiumtribromide (0.5 mol %) was added to a solution of 2-amino benzanilide or 2-amino-5-chloro benzamide (1 mmol) and desired aldehydes (1 mmol) in acetonitrile (3mL). The mixture was stirred at room temperature for the specified period of time. The progress of the reaction was monitored by TLC. After completion of reaction, solvent was evaporated at reduced pressure, and solid was partitioned between ethyl acetate (15.0 mL) and water (15.0mL), and transferred to a separatory funnel. The organic layer was washed with water, and brine, dried over anhydrous Na2SO4 (s) and concentrated in vacuo. The residue was purified by recrystallization from CH2Cl2/Hexane to afford the corresponding pure 2,3-dihydroquinazolin-4(1H)-ones (3a-3aa) as solids with excellent yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With indium(III) bromide In acetonitrile at 20℃; for 0.5h; | 1.2 General Procedure for Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones (3a-3aa) General procedure: Indiumtribromide (0.5 mol %) was added to a solution of 2-amino benzanilide or 2-amino-5-chloro benzamide (1 mmol) and desired aldehydes (1 mmol) in acetonitrile (3mL). The mixture was stirred at room temperature for the specified period of time. The progress of the reaction was monitored by TLC. After completion of reaction, solvent was evaporated at reduced pressure, and solid was partitioned between ethyl acetate (15.0 mL) and water (15.0mL), and transferred to a separatory funnel. The organic layer was washed with water, and brine, dried over anhydrous Na2SO4 (s) and concentrated in vacuo. The residue was purified by recrystallization from CH2Cl2/Hexane to afford the corresponding pure 2,3-dihydroquinazolin-4(1H)-ones (3a-3aa) as solids with excellent yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With yttrium(III) trifluoromethanesulfonate In dimethyl sulfoxide at 110℃; | 2.2 A general procedure for preparation of quinazolinones 4 General procedure: Y(OTf)3 (0.0268 g, 0.05 mmol) were dissolved in 10 mL DMSO and stirred until the solid dissolved completely, then anthranilamide 1a (0.1498 g, 1.1 mmol) and benzaldehyde 2a (0.101 mL, 1.0 mmol) was added into the reaction mixture. Then the mixture was heated at 110 under air atmosphere. After completion of the reaction, as indicated by TLC, the reaction mixture was cooled to room temperature. Water (15 mL) was added to the reaction mixture, and the crystalline products were collected by filtration to give the crude product. The crude products thus obtained were crystallized from EtOH to give pure products 4a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With yttrium(III) trifluoromethanesulfonate In dimethyl sulfoxide at 110℃; | 2.2 A general procedure for preparation of quinazolinones 4 General procedure: Y(OTf)3 (0.0268 g, 0.05 mmol) were dissolved in 10 mL DMSO and stirred until the solid dissolved completely, then anthranilamide 1a (0.1498 g, 1.1 mmol) and benzaldehyde 2a (0.101 mL, 1.0 mmol) was added into the reaction mixture. Then the mixture was heated at 110 under air atmosphere. After completion of the reaction, as indicated by TLC, the reaction mixture was cooled to room temperature. Water (15 mL) was added to the reaction mixture, and the crystalline products were collected by filtration to give the crude product. The crude products thus obtained were crystallized from EtOH to give pure products 4a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With yttrium(III) trifluoromethanesulfonate In dimethyl sulfoxide at 110℃; | 2.2 A general procedure for preparation of quinazolinones 4 General procedure: Y(OTf)3 (0.0268 g, 0.05 mmol) were dissolved in 10 mL DMSO and stirred until the solid dissolved completely, then anthranilamide 1a (0.1498 g, 1.1 mmol) and benzaldehyde 2a (0.101 mL, 1.0 mmol) was added into the reaction mixture. Then the mixture was heated at 110 under air atmosphere. After completion of the reaction, as indicated by TLC, the reaction mixture was cooled to room temperature. Water (15 mL) was added to the reaction mixture, and the crystalline products were collected by filtration to give the crude product. The crude products thus obtained were crystallized from EtOH to give pure products 4a. |
86% | With tert.-butylhydroperoxide; fluorescein In methanol at 20℃; for 3h; Irradiation; Green chemistry; | |
81% | With bismuth (III) nitrate pentahydrate In ethanol at 60℃; for 12h; | General experimental procedure for oxidative cyclocondensation of 2-aminobenzamidewith aldehydes General procedure: To a 100 mL round bottom flask fitted with a condenser containing magnetic stir bar, 1a (0.5mmol), 2a (1.2 equiv, 0.6 mmol), Bi(NO2)3• 5H2O (10 mol%), and ethanol (5 mL) were added.The resultant mixture was stirred at 60 °C under open-air condition for 12 h. The reactionmixture was cooled to rt, and subjected to crystallization (EtOH) to get analytically pure 2-phenyl-3H-quinazolin-4-one 3a (91%); 1H NMR (400 MHz, DMSO-d6) δ 12.55 (s, 1H), 8.28 - 8.10(m, 3H), 7.83 (ddd, J = 8.5, 6.4, 1.7 Hz, 1H), 7.75 (d, J = 8.2 Hz, 1H), 7.67 - 7.47 (m, 4H); 13C NMR(100 MHz, DMSO-d6) δ 162.7, 152.8, 149.2, 135.0, 133.2, 131.8, 129.1, 128.2, 127.9, 127.0,126.3, 121.4; Mass (ESI) m/z: = 222.1(M+). |
73% | With dimethyl sulfoxide at 20℃; for 18h; Irradiation; Green chemistry; | |
Multi-step reaction with 2 steps 1: water / 2 h / Reflux 2: C5H11IrO3(2+)*2CF3O3S(1-) / water / 1 h / Reflux | ||
With oxygen In dimethyl sulfoxide; N,N-dimethyl-formamide at 120℃; for 5h; | 2.2 Catalytic studies General procedure: In a typical experiment, a solution of phenylacetic acid (0.3mmol, 40.8mg) in DMF (0.5mL) was added to a 10mL vial with the VNU-21 catalyst (5.5mg, 5mol%). The mixture was stirred at 120°C for 4h under an oxygen atmosphere. After that, the catalyst was removed by filtration. A solution of 2-aminobenzamide (0.2mmol, 27.2mg) in DMSO (0.5mL) was then added to the reactor. The mixture was additionally stirred at 120°C for 5h under oxygen. The GC yield of benzaldehyde and 2-phenylquinazolin-2(3H)-one were monitored by withdrawing samples from the reaction mixture, quenching with brine (1mL), extracting with ethyl acetate (3×1mL), drying over anhydrous Na2SO4, and analyzing by GC regarding diphenyl ether as internal standard. After the completion of the second step, the reaction mixture was cooled to room temperature. Resulting solution was quenched with brine (5mL), extracted by ethyl acetate (3×5mL), dried over anhydrous Na2SO4 prior to the removal of solvent under vacuum. The crude product was purified by silica gel column chromatography using hexane and ethyl acetate (1:1, v/v) as eluent. The structure of 2-phenylquinazolin-4(3H)-one was verified by GC-MS, 1H NMR and 13C NMR. For the leaching test, after the first 4h reaction time, the catalyst was removed by filtration. The solution phase was transferred to a new and clean reactor. New phenylacetic acid was added, and the resulting mixture was subsequently stirred for additional 4h at 120°C under an oxygen atmosphere. The yield of benzaldehyde was monitored by GC. | |
With oxygen In dimethyl sulfoxide at 120℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With yttrium(III) trifluoromethanesulfonate In dimethyl sulfoxide at 110℃; | 2.2 A general procedure for preparation of quinazolinones 4 General procedure: Y(OTf)3 (0.0268 g, 0.05 mmol) were dissolved in 10 mL DMSO and stirred until the solid dissolved completely, then anthranilamide 1a (0.1498 g, 1.1 mmol) and benzaldehyde 2a (0.101 mL, 1.0 mmol) was added into the reaction mixture. Then the mixture was heated at 110 under air atmosphere. After completion of the reaction, as indicated by TLC, the reaction mixture was cooled to room temperature. Water (15 mL) was added to the reaction mixture, and the crystalline products were collected by filtration to give the crude product. The crude products thus obtained were crystallized from EtOH to give pure products 4a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With ytterbium(III) triflate; In 1,3,5-trimethyl-benzene; at 60℃; for 24h;Inert atmosphere; | General procedure: 2-aminobenzamide (1, 1.0 mmol), 1,3-diketone (2, 1.5 mmol), Yb(OTf)3 (0.050 mmol, 5.0 molpercent),and mesitylene (2.0 mL) was placed in a 20-mL Pyrex flask equipped with a magnetic stirring bar and a reflux condenser under a flow of argon. The reaction was carried out at 60°C (bath temp.) for 24 h with stirring. The reaction mixture was then cooled to room temperature and analyzed by GLCand GC-MS. The product 3 was isolated by medium-pressure column chromatography on silica gel(eluent: EtOAc/hexane = 30/70 ~ EtOAc 100percent. For 3j, eluent: MeOH/CHCl3 = 30/70 ~ 50/50) andrecrystallization from MeOH/hexane. The products 3l and 3m were isolated by recrystallizationfrom EtOAc/hexane. 1H NMR spectra were recorded at 400 MHz, and 13C NMR spectra wererecorded at 100 MHz in DMSO-d6 (For 3j, in a mixture of DMSO-d6 and methanol-d4). Elemental analyses were performed at the Microanalytical Center of Kyoto University. The analytical and spectral data of 3a,10 3b-c,11 3d,12 3e,13 3f,14 3g-h,10 and 3j-l,7 are fully consistent with those reported previously. The products 3i,15 and 3m16 were characterized below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With [Cp*Ir(2,2'-bpyO)(H2O)]; caesium carbonate; at 130℃; for 2h;Inert atmosphere; Microwave irradiation; | 2-Amino-5-chlorobenzamide (85 mg, 0.5 mmol), [Cp * Ir (2,2'-bpyO) (H2O)](5.4 mg, 0.005 mmol, 1 mol%),Cesium carbonate (49 mg, 0.15 mmol, 0.3 equiv.) And methanol (0.5 ml) were sequentially added to a dried 5 mL microwave reaction tube.The tube was nitrogen protected and placed in a single mode pressure microwave synthesizer (Discover CEM, USA). After the reaction mixture was reacted at 130 C for 2 hours, it was cooled to room temperature. Rotary evaporation to remove the solvent,Pure target compound was then obtained by column chromatography (developing solvent: petroleum ether / ethyl acetate), yield: 77% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With lithium bromide monohydrate In nitromethane at 100℃; for 4h; | 3.6. Reaction procedure for the synthesis of 11a General procedure: 3.6. Reaction procedure for the synthesis of 11a The reactions was conducted in a 10 mL of V-type ask equippedwith triangle magnetic stirring. In a typical reaction,1a (0.20 mmol)was mixed with 9a (0.20 mmol) and LiBrH2O (30 mol %) in ni-tromethane (1.0 mL). The mixture was then stirred at 100 C for 4 h.After reaction, 11a was obtained by isolation with preparative TLC(eluting solution: petroleum ether/ethyl acetate1/1 (v/v)) in 56%(0.112 mmol, 29.1 mg) yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | In water at 70℃; for 2h; | General Procedure for the Synthesis of 2-(nitromethyl)quinazolin-4(1H)-ones (3a-3l) General procedure: 2-Aminobenzamides (1 mmol) and 1,1-dichloro-2-nitroethene (1.2 mmol) were added to 5 mL of water in a 25 mL round-bottom flask. Then stirred at corresponding temperature and corresponding reaction time, after completion, the product precipitated from the reaction mixture and can be easily separated by filtration, then give the pure products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With triethylamine In tetrahydrofuran at 0 - 20℃; Inert atmosphere; | Synthesisof 2-(4-chlorobutanamido)-benzamides: general procedure A General procedure: Asolutionoftheappropriatesubstituted2-aminobenzamide(1.0eq)inTHF(2.5mLpermmolsubstrate)wascooledto0°Candtriethylamine(2.0eq)thentheappropriateacidchloride(1.2eq)inTHF(2mLpermmolsubstrate)wereaddedtothestirredsolution.ThereactionwasstirredatroomtemperatureuntilcompletionasindicatedbyTLC,whenthemixturewasdilutedwithEtOAcandquenchedwithNaHSO4(20mL).TheaqueousphasewasextractedwithEtOAc(320mL),combinedorganicphasesdriedoverMgSO4,excesssolventremovedinvacuoandtheresiduepurifiedbyFCC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With oxygen; In dimethyl sulfoxide; at 120℃; under 760.051 Torr; for 12h;Schlenk technique; Sealed tube; Green chemistry; | General procedure: A 25 mL Schlenk-type tube equipped with a magnetic stir bar was charged with o-substituted aniline 1a-1f. The reaction tube was evacuated and back-filled with O2. Under oxygen atmospheres, ethers or alcohols 2a-2n and DMSO were added at room temperature, then the reaction mixture was stirred at 120 C for 12 h. The reaction was monitored by TLC. After completion of the reaction, the resulting solution was cooled to room temperature, and neutralized with saturated NaHCO3 aqueous solution. The product was extracted with EtOAc or CHCl3, dried over anhydrous Na2SO4 and concentrated in vacuum. The crude product was purified by flash column chromatography on silica gel to give N-heterocyclic compounds 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; | General procedure: To a solution of PTMA (1d) (29.0 mg, 0.10 mmol) and aminobenzoates 2 (1.5 mmol or 0.20 mmol) in DMF (1.0 mL) at room temperature were added Et3N or pyridine (0.42 mmol) and HATU(76.1 mg, 0.20 mmol). The mixture was stirred at room temperature overnight and monitored by TLC. Then brine (10 mL) was added.The resulting mixture was extracted with EtOAc (3 5.0 mL), and the combined organic portions were dried over anhydrous sodium sulfate and concentrated in vacuo. compounds 3 were finally prepared through flash column chromatography (eluent: EtOAc/lightpetroleum ether 1:20e5:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | In ethanol; for 0.166667h;Microwave irradiation; | General procedure: To a stirred solution of <strong>[131805-94-2]1-[3,5-bis(trifluoromethyl)phenyl]-2-bromoethan-1-one</strong> (2) (0.5 mmol) in absolute ethanol (10 mL) was added substituted alkyl, aryl and heteroaryl amides (1) (0.5 mmol) and exposed to microwaves for 10 min (Table-1).The reaction medium was cooled to room temperature and poured into 12 mL of 10 % sodium acetate solution. The precipitate obtained from the reaction medium was separated by filtration and the crude product was recrystallized from ethanol. The yield of the title compounds was found to be in the range of 86-98 % |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)] In toluene at 120℃; for 12h; Inert atmosphere; | 221 6-chloro-2-phenethylquinazolin-4(3H)-one Under nitrogen atmosphere, 2-amino-5-chlorobenzamide (171 mg, 1 mmol), [Cp*IrCl2]2 (8 mg, 0.01 mmol, 1 mol%), toluene (1.0 mL), cinnamaldehyde (132 mg, 1 mmol)Add 25mL Schlenk reaction flasks one by one.The mixture was reacted at 120°C for 12 hours and then cooled to room temperature.The solvent was removed in vacuo under reduced pressure and then purified by column chromatography (developer: ethyl acetate/petroleum ether) to give the pure target compound, yield: 84%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With copper(II) oxide; In N,N-dimethyl acetamide; at 120℃; for 24h; | General procedure: A mixture of 3a-3d, 3t or 3w (1mmol), 4a (172mg, 1mmol) and CuO (4mg, 0.05mmol) in DMA (3mL) was heated at 120C for 24h. The mixture was cooled to room temperature and extracted with EtOAc three times. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography eluting with CH2Cl2/MeOH (30/1) to afford B3-B8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With 1,3,5-trichloro-2,4,6-triazine; In acetonitrile; at 20℃; | General procedure: Cyanuric chloride (0.15mmol) was added to a mixture of 3a-3x (1mmol) and 4a (206mg, 1.2mmol) in CH3CN, MeOH or DMSO (3mL). The mixture was stirred at room temperature for 0.5-2h. After completion, the mixture was extracted with EtOAc three times. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography eluting with CH2Cl2/MeOH (30/1) to afford H1, A1-A23. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 120℃; for 20h; Inert atmosphere; Autoclave; | 4.3 General procedure for the heterogeneous palladium-catalyzed carbonylative synthesis of quinazolinones General procedure: A 12mL vial was charged with MCM-41-2P-Pd(OAc)2 (2mol%), 2-aminobenzamide (1mmol), aryl iodide (1mmol) (if solid) and a stirring bar. Then, DMF (2mL), aryl iodide (1mmol) (if liquid) and DBU (2mmol) were injected by syringe under an argon atmosphere. The vial was placed in an alloy plate, which was transferred into a 300mL Parr Instruments 4560 series autoclave under an argon atmosphere. After flushing the autoclave three times with CO, a pressure of 10bar CO was fixed at ambient temperature. The autoclave was heated for 20hat 120°C. After completion of the reaction, the autoclave was cooled to room temperature and the pressure was released carefully. The reaction mixture was diluted with ethyl acetate (10mL) and filtered. The palladium catalyst was washed with distilled water (2×5mL) and acetone (2×5mL), and reused in the next run. The filtrate was concentrated in vacuo and the pure product was isolated by either washed with water, ethyl acetate and finally hexane or recrystallization from MeOH. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 120℃; for 20h; Inert atmosphere; Autoclave; | 4.3 General procedure for the heterogeneous palladium-catalyzed carbonylative synthesis of quinazolinones General procedure: A 12mL vial was charged with MCM-41-2P-Pd(OAc)2 (2mol%), 2-aminobenzamide (1mmol), aryl iodide (1mmol) (if solid) and a stirring bar. Then, DMF (2mL), aryl iodide (1mmol) (if liquid) and DBU (2mmol) were injected by syringe under an argon atmosphere. The vial was placed in an alloy plate, which was transferred into a 300mL Parr Instruments 4560 series autoclave under an argon atmosphere. After flushing the autoclave three times with CO, a pressure of 10bar CO was fixed at ambient temperature. The autoclave was heated for 20hat 120°C. After completion of the reaction, the autoclave was cooled to room temperature and the pressure was released carefully. The reaction mixture was diluted with ethyl acetate (10mL) and filtered. The palladium catalyst was washed with distilled water (2×5mL) and acetone (2×5mL), and reused in the next run. The filtrate was concentrated in vacuo and the pure product was isolated by either washed with water, ethyl acetate and finally hexane or recrystallization from MeOH. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 12h; | 21 An aromatic amine 1q-1 (0.20 mmol) and a platensimycin acid (0.10 mmol) were weighed.2-(7-Azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU) (0.30 mmol) was added to the reaction flask and 1.0 ml was added.N,N-dimethylformamide, stirring at room temperature; slowly adding triethylamine (0.45 mmol), stirring for 12 hours, rotary evaporationSolvent to obtain a crude product, which is subjected to column chromatography to obtain a platensimycin analog2q-1, yield 46%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With acetic acid In ethanol at 110℃; for 24h; Inert atmosphere; Sealed tube; | 3.2.2. Method 2 General procedure: The 2-aminobenzamide (1 equiv), the orthoester (2-3 equiv) and absolute ethanol (2-3 mL) wereplaced in a 15-mL Chemglass screw-cap pressure tube (No. CG-1880-01, Chemglass, Vineland, NJ,USA). Glacial acetic acid (3 equiv) was added, N2 was introduced to the vessel and the cap wastightened. The vessel was heated at 110 °C for 12-72 h, then cooled and concentrated to give thequinazolinone, which was purified by crystallization from absolute ethanol or trituration from 5%ether in pentane. The following compounds were prepared: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With acetic acid; In ethanol; at 110℃; for 24h;Inert atmosphere; Sealed tube; | General procedure: The 2-aminobenzamide (1 equiv), the orthoester (2-3 equiv) and absolute ethanol (2-3 mL) wereplaced in a 15-mL Chemglass screw-cap pressure tube (No. CG-1880-01, Chemglass, Vineland, NJ,USA). Glacial acetic acid (3 equiv) was added, N2 was introduced to the vessel and the cap wastightened. The vessel was heated at 110 C for 12-72 h, then cooled and concentrated to give thequinazolinone, which was purified by crystallization from absolute ethanol or trituration from 5%ether in pentane. The following compounds were prepared: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With acetic acid In ethanol at 110℃; for 24h; Inert atmosphere; Sealed tube; | 3.2.2. Method 2 General procedure: The 2-aminobenzamide (1 equiv), the orthoester (2-3 equiv) and absolute ethanol (2-3 mL) wereplaced in a 15-mL Chemglass screw-cap pressure tube (No. CG-1880-01, Chemglass, Vineland, NJ,USA). Glacial acetic acid (3 equiv) was added, N2 was introduced to the vessel and the cap wastightened. The vessel was heated at 110 °C for 12-72 h, then cooled and concentrated to give thequinazolinone, which was purified by crystallization from absolute ethanol or trituration from 5%ether in pentane. The following compounds were prepared: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With acetic acid; In ethanol; at 110℃; for 24h;Inert atmosphere; Sealed tube; | General procedure: The 2-aminobenzamide (1 equiv), the orthoester (2?3 equiv) and absolute ethanol (2?3 mL) wereplaced in a 15-mL Chemglass screw-cap pressure tube (No. CG-1880-01, Chemglass, Vineland, NJ,USA). Glacial acetic acid (3 equiv) was added, N2 was introduced to the vessel and the cap wastightened. The vessel was heated at 110 °C for 12?72 h, then cooled and concentrated to give thequinazolinone, which was purified by crystallization from absolute ethanol or trituration from 5percentether in pentane. The following compounds were prepared: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With ammonium hydroxide; dihydrogen peroxide In dimethyl sulfoxide at 20 - 30℃; for 4h; Sealed tube; | 5.2 Representative procedure for the synthesis of 4 (A) General procedure: A sealed tube was charged with isatin 1 (1a 147 mg, 1.0 mmol), ammonia hydrate 2 (25%, 421 mg, 3.0 mmol) and H2O2 (30%, 227 mg, 2.0 mmol) at room temperature, and then solvent DMSO (4 mL) was added. The resulting mixture was stirred at 30 °C in a sealed vessel under air after 4 h, then added 50 mL water to the mixture, extracted with CH3COOC2H5 3 times (3 x 50 mL). The extract was washed with 30% NaCl solution (V/V), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (Petroleum ether/Ethyl acetate = 3:1) to yield the desired product 3a as a yellow solid (89% yield). |
61% | With ammonia In methanol; acetonitrile at 20℃; for 5h; Electrolysis; | |
Multi-step reaction with 2 steps 1.1: sodium hydroxide / lithium hydroxide monohydrate / 70 °C 1.2: 0.83 h / 70 °C 2.1: N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride; benzotriazol-1-ol; 4-methyl-morpholine / tetrahydrofuran / 0.17 h 2.2: 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With [(p‑cymene)Ru(2,2′-bpyO)(H2O)] In tetrahydrofuran at 130℃; for 3h; | 9 Example 9: 2-Ethyl-6-chloroquinazoline-4(3H)-one 2-Amino-5-chlorobenzamide (85 mg, 0.5 mmol),Ruthenium catalyst (4.4 mg, 0.01 mmol, 2 mol%), THF (0.5 mL),Propylene alcohol (34.8 mg, 0.6 mmol) was sequentially added to the microwave reaction tube.The mixture was reacted at 130 ° C for 3 hours and then cooled to room temperature.The solvent was removed under reduced pressure in vacuo and then purified by column chromatography (eluent: ethyl acetate / petroleumEther) gave the pure title compound in a yield: 90%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: 2-Amino-5-chlorobenzamide With {10,16-bis[3,5-bis(trifluoromethyl)phenyl]-13-hydroxy-13-oxo-12,14-dioxa-13l^{5}-phosphapentacyclo[13.8.0.0^{2,11}.0^{3,8}.0^{18,23}]tricosa-1(15),2(11),3,5,7,9,16,18,20,22-decaen-6-yl}methyl benzenesulfonate, polymer bound In chloroform for 0.166667h; Stage #2: benzaldehyde N-boc imine In chloroform at -15℃; for 30h; enantioselective reaction; | 2.3 General Procedure for the EnantioselectitiveSynthesis of 2, 3-DHQZs General procedure: 2-aminobenzamide 2 (1.0 mmol) was added to a suspensionof the catalyst 5 (2.1 mmol/g, 0.05 g, 0.1 mmol) inCHCl3 (10 mL) and stirred for 10 min, followed by N-Bocimines 1 (1.1 mmol) and stirred at -15 C for 24-36 h, thereaction was ascertained by TLC. When the reaction wascompleted, the mixture was filtered and washed severaltimes with CHCl3. The filtrate was concentrated and purifiedby silica gel chromatography to obtain pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With dimethyl sulfoxide; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide at 20℃; for 4h; Green chemistry; | General Procedure for the synthesis of o-ureidobenzonitriles (3a-3t) General procedure: The mixture of o-aminobenzamide (1) (1 mmol) and isothiocyanates (2) (1 mmol) was allowed to stir in DMSO solvent and T3P (Propane phosphonic acid anhydride solution: 50 wt. % in ethyl acetate) reagent (1 mmol, 0.7 g) at room temperature for 4 h in a round bottomed flask. After that, the contents of the flask were poured in to 15 ml of water taken in separating funnel and extracted to 15 ml ethyl acetate. The ethyl acetate extract was separated and dried over anhydrous sodium sulfate. The solvent was then removed under reduced pressure to afford corresponding o-ureidobenzonitrile (3). The crude residue thus obtained was purified by column chromatography over silica gel using 10 % ethyl acetate in hexane as eluent to afford the pure o-ureidobenzonitrile with 80-95% yields. |
80% | With iodine In N,N-dimethyl-formamide at 20℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With dimethyl sulfoxide; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide at 20℃; for 4h; Green chemistry; | General Procedure for the synthesis of o-ureidobenzonitriles (3a-3t) General procedure: The mixture of o-aminobenzamide (1) (1 mmol) and isothiocyanates (2) (1 mmol) was allowed to stir in DMSO solvent and T3P (Propane phosphonic acid anhydride solution: 50 wt. % in ethyl acetate) reagent (1 mmol, 0.7 g) at room temperature for 4 h in a round bottomed flask. After that, the contents of the flask were poured in to 15 ml of water taken in separating funnel and extracted to 15 ml ethyl acetate. The ethyl acetate extract was separated and dried over anhydrous sodium sulfate. The solvent was then removed under reduced pressure to afford corresponding o-ureidobenzonitrile (3). The crude residue thus obtained was purified by column chromatography over silica gel using 10 % ethyl acetate in hexane as eluent to afford the pure o-ureidobenzonitrile with 80-95% yields. |
78% | With iodine In N,N-dimethyl-formamide at 20℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With dimethyl sulfoxide; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide at 20℃; for 4h; Green chemistry; | General Procedure for the synthesis of o-ureidobenzonitriles (3a-3t) General procedure: The mixture of o-aminobenzamide (1) (1 mmol) and isothiocyanates (2) (1 mmol) was allowed to stir in DMSO solvent and T3P (Propane phosphonic acid anhydride solution: 50 wt. % in ethyl acetate) reagent (1 mmol, 0.7 g) at room temperature for 4 h in a round bottomed flask. After that, the contents of the flask were poured in to 15 ml of water taken in separating funnel and extracted to 15 ml ethyl acetate. The ethyl acetate extract was separated and dried over anhydrous sodium sulfate. The solvent was then removed under reduced pressure to afford corresponding o-ureidobenzonitrile (3). The crude residue thus obtained was purified by column chromatography over silica gel using 10 % ethyl acetate in hexane as eluent to afford the pure o-ureidobenzonitrile with 80-95% yields. |
78% | With iodine In N,N-dimethyl-formamide at 20℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With dimethyl sulfoxide; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide at 20℃; for 4h; Green chemistry; | General Procedure for the synthesis of o-ureidobenzonitriles (3a-3t) General procedure: The mixture of o-aminobenzamide (1) (1 mmol) and isothiocyanates (2) (1 mmol) was allowed to stir in DMSO solvent and T3P (Propane phosphonic acid anhydride solution: 50 wt. % in ethyl acetate) reagent (1 mmol, 0.7 g) at room temperature for 4 h in a round bottomed flask. After that, the contents of the flask were poured in to 15 ml of water taken in separating funnel and extracted to 15 ml ethyl acetate. The ethyl acetate extract was separated and dried over anhydrous sodium sulfate. The solvent was then removed under reduced pressure to afford corresponding o-ureidobenzonitrile (3). The crude residue thus obtained was purified by column chromatography over silica gel using 10 % ethyl acetate in hexane as eluent to afford the pure o-ureidobenzonitrile with 80-95% yields. |
80% | With iodine In N,N-dimethyl-formamide at 20℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With tetrabutylammonium tetrafluoroborate In acetonitrile at 80℃; for 6h; Electrochemical reaction; | Quinazolinones 3a-q; General Procedure General procedure: A mixture of the appropriate 2-aminobenzamide 1 (0.5 mmol),benzylic chloride 2 (0.6 mmol), and Bu4NBF4 (10 mol%) wasplaced in a 25 mL three-necked round-bottomed flask equippedwith a condenser, an RVC (100 PPI) anode, and a Pt plate (1 × 1cm) cathode. The flask was opened to air and MeCN (6 mL) wasadded. Electrolysis was carried out at 80 °C (oil-bath temperature)at a constant current of 10 mA until the substrate wascompletely consumed (TLC). The mixture was then cooled to rt,and the solvent was removed under reduced pressure. Theresidue was purified by chromatography (silica gel, EtOAc-PE). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With Imidazole hydrochloride at 150℃; for 13h; | 4.1.1 General procedures for the synthesis of 4(3H)-quinazolinones 3a-3g, 3o-3v General procedure: A mixture of anthranilamide 1 (0.5g, 3.67mmol, 1 equiv.), DMF (2ml) and imidazolium chloride (2.5 equiv.) was stirred in a round-bottom flask at 150°C under reflux for 13 h. When the reaction reached completion, reduced the temperature to 80°C, extra 2ml DMF was added to dissolve the reaction mixture, then, a saturated solution of NaCl (25ml) was added. The aqueous phase was extracted with ethyl acetate (4×20mL), and dried over anhydrous Na2SO4 and concentrated in vacuum with silica gel added. The residue was purified by flash chromatography (petroleum ether/ethyl acetate) to obtain the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With Candida antarctica lipase B In hexane; water at 50℃; for 40h; Enzymatic reaction; | General experimental procedure for the synthesis of quinazolinones. Path A: General procedure: A 10-mL stoppered bottle was filled with the required 2-aminobenzamide (0.2 mmol), dicarbonyl compound (0.5 mmol), CALB (10U), 2 mL solvent (ratio of hexane to water was 2:1) and oscillate in a constant temperature shaker at 50 °C for 40 h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With α-chymotrypsin In ethanol at 60℃; for 40h; Enzymatic reaction; | Path B: General procedure: A 10-mL stoppered bottle was filled with the required 2-aminobenzamide (0.2 mmol), dicarbonyl compound (0.6 mmol), α-chymotrypsin (2400U), 2 mL EtOH and oscillate in a constant temperature shaker at 60 °C for 40 h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With Candida antarctica lipase B In hexane; water at 50℃; for 40h; Enzymatic reaction; | General experimental procedure for the synthesis of quinazolinones. Path A: General procedure: A 10-mL stoppered bottle was filled with the required 2-aminobenzamide (0.2 mmol), dicarbonyl compound (0.5 mmol), CALB (10U), 2 mL solvent (ratio of hexane to water was 2:1) and oscillate in a constant temperature shaker at 50 °C for 40 h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With α-chymotrypsin In ethanol at 60℃; for 40h; Enzymatic reaction; | Path B: General procedure: A 10-mL stoppered bottle was filled with the required 2-aminobenzamide (0.2 mmol), dicarbonyl compound (0.6 mmol), α-chymotrypsin (2400U), 2 mL EtOH and oscillate in a constant temperature shaker at 60 °C for 40 h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With α-chymotrypsin In ethanol at 60℃; for 40h; Enzymatic reaction; | Path B: General procedure: A 10-mL stoppered bottle was filled with the required 2-aminobenzamide (0.2 mmol), dicarbonyl compound (0.6 mmol), α-chymotrypsin (2400U), 2 mL EtOH and oscillate in a constant temperature shaker at 60 °C for 40 h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With α-chymotrypsin In ethanol at 60℃; for 40h; Enzymatic reaction; | Path B: General procedure: A 10-mL stoppered bottle was filled with the required 2-aminobenzamide (0.2 mmol), dicarbonyl compound (0.6 mmol), α-chymotrypsin (2400U), 2 mL EtOH and oscillate in a constant temperature shaker at 60 °C for 40 h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With copper(l) iodide; potassium carbonate In dimethyl sulfoxide at 100℃; for 6h; | In DMSO, I2 (1.5 equivalents),In the presence of CuI (0.3 equivalent) and K2CO3 (1 equivalent), 2-amino-5-chlorobenzamide reacts with 1-(2-bromo-5-chlorophenyl)ethan-1-one at 100°C for 6 hours , The intermediate M1 was obtained with a yield of 70%. |
70% | With copper(l) iodide; iodine; potassium carbonate In dimethyl sulfoxide at 100℃; for 6h; | In DMSO, in the presence of I2 (1.5 equivalent), CuI (0.3 equivalent), and K2CO3 (1 equivalent),2-Amino-5-chlorobenzamide and 1-(2-bromo-5-chlorophenyl)ethan-1-one were reacted at 100°C for 6 hours to obtain intermediate M1 with a yield of 70%.(The preparation method reference: International Journal of Pharma Research and Health Sciences, 2018; 6(6): 2865-68). |
70% | With iodine; potassium carbonate In dimethyl sulfoxide at 100℃; for 6h; | In DMSO, in the presence of I2 (1.5 equivalent), CuI (0.3 equivalent), and K2CO3 (1 equivalent),2-Amino-5-chlorobenzamide and 1-(2-bromo-5-chlorophenyl)ethan-1-one were reacted at 100°C for 6 hours to obtain intermediate M1 with a yield of 70%.(The preparation method reference: International Journal of Pharma Research and Health Sciences, 2018; 6(6): 2865-68). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With copper(l) iodide; iodine; potassium carbonate In dimethyl sulfoxide at 100℃; for 6h; | In DMSO, in the presence of I2 (1.5 equivalent), CuI (0.3 equivalent), 2CO3 (1 equivalent), 2-amino-5-chlorobenzoyl Amine and 1- (2-bromo-5-chlorophenyl) ethyl-1-one were reacted at 100°C for 6 hours to obtain intermediate M1 with a yield of 70%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With Sodium borate In water at 100℃; for 14h; | General procedure for the synthesis of quinazolin-4(3H)-one/benzothiadiazine 1,1-dioxides/benzothiazole/benzoxazoles General procedure: 2-Aminobenzamide/2-aminobenzenesulfonamide/2-aminothiophenol/2-aminophenol (0.3mmol), α,α,α-trichlorotoluene (0.36mmol), and borax (4 equiv) were taken in a 50ml round bottom flask, and the reaction mixture was stirred in H2O (3ml) at 100 for a period of the time till the completion of the reaction (monitored by TLC). After completion of the reaction, it was extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography to give the desired product. All compounds were well characterized by FT-IR, 1H, 13C NMR, and melting point analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With iodine In dimethyl sulfoxide at 110℃; | 4.1.2. General procedures to synthesize 4a-4u General procedure: I2 (362.25 mg, 1.43 mmol, 1.1 eq) was added to a mixture of 2j(272.77 mg, 1.3 mmol, 1 eq) and DMSO (3 mL). The solution wasstirred at 110°C, then 1a1u (1 eq) in 3 mL DMSO was addeddropwise to the mixture during 1 h. After the complete disappearanceof the starting material, a sodium thiosulfate solution(0.2 g Na2S2O3 in 12 mL water) was added dropwise to the reactionsystem. Filtration and drying, the residue was purified by silica gelchromatography to yield the desired products 4a-4u. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; | General procedure (GP1) for the synthesis of amides 10 General procedure: To a solution of amine 8 (1.5 mmol) and triethylamine (0.15 g, 1.5 mmol) in DMF (10 mL),allylacetyl chloride 9 (0.18 g, 1.5 mmol) was added dropwise at 0 C. The resulting mixturewas stirred at rt for 3-4 h and then left overnight. The solvent was removed in vacuo, and theresidue was triturated with H2O (20 mL). The crystalline product 10 formed was filtered, dried,and used in the next without additional purification. An analytical sample was obtained byiPrOH or t-BuOMe. |
Tags: 5202-85-7 synthesis path| 5202-85-7 SDS| 5202-85-7 COA| 5202-85-7 purity| 5202-85-7 application| 5202-85-7 NMR| 5202-85-7 COA| 5202-85-7 structure
[ 890707-28-5 ]
2-Amino-5-chloro-N,3-dimethylbenzamide
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[ 890707-28-5 ]
2-Amino-5-chloro-N,3-dimethylbenzamide
Similarity: 0.84
[ 890707-28-5 ]
2-Amino-5-chloro-N,3-dimethylbenzamide
Similarity: 0.84
[ 890707-28-5 ]
2-Amino-5-chloro-N,3-dimethylbenzamide
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H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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