6-Chloro-4(3H)-quinazolinone

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.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: 77percentExamples 13 to 21:; The reaction and the post-treatment were carried out in the same manner as in Example 5, for which, however, the type of the anthranilic acid derivative was changed. The results are shown in Table 4.General procedure: To a three necked flask, substituted anthranilic acid (1 meq.) was added in excess of formamide (6 meq). The reaction mixture was then heated at 140 °C for 4-6 h. The reaction was monitored with thin layer chromatography and upon completion; ice was added to the reaction mixture. The resultant solid was filtered, washed with water, dissolved in ethyl acetate, dried over MgSOGeneral 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.Examples 13 to 21:; The reaction and the post-treatment were carried out in the same manner as in Example 5, for which, however, the type of the anthranilic acid derivative was changed. The results are shown in Table 4.Examples 13 to 21:; The reaction and the post-treatment were carried out in the same manner as in Example 5, for which, however, the type of the anthranilic acid derivative was changed. The results are shown in Table 4.General procedure: To a three necked flask, substituted anthranilic acid (1 meq.) was added in excess of formamide (6 meq). The reaction mixture was then heated at 140 C for 4-6 h. The reaction was monitored with thin layer chromatography and upon completion; ice was added to the reaction mixture. The resultant solid was filtered, washed with water, dissolved in ethyl acetate, dried over MgSO4 and concentrated to obtain the pure desired product. Where product did not precipitate on addition of ice, the reaction mixture was extracted with ethyl acetate, dried over MgSO4 and concentrated to obtain the desired quinazolin-4(3H)-one derivatives 1-9, 11-15, 17-21 and 23-25.The amino derivatives 10, 16 and 22 were prepared using the following general procedure:To a reaction flask, substituted nitroquinazolin-4(3H)-one derivative (0.3 g, 1.56 mmol) was added followed by addition of 6 mL ethyl acetate and SnCl2·2H2O (2.12 g, 9.42 mmol), then reaction mixture was refluxed for 8 h. The reaction mixture was cooled to room temperature and quenched with saturated sodium bicarbonate solution, followed by repeated extraction with ethyl acetate (3 × 50 mL). The organic layers were combined, dried over anhydrous MgSO4 and concentrated to obtain the desired amino substituted quinazolin-4(3H)-one derivatives 10, 16 and 22.The substituted anthranilic acid (1 g) was dissolved in excess acetic anhydride (10 mL) and the resulting reaction mixture was stirred at room temperature for 4-7 h. The reaction was monitored for completion using thin layer chromatography. The solvent was evaporated under vacuum and the resultant residue was stirred with ammonia solution for 7 h. Upon completion, the reaction mixture was extracted with ethyl acetate (3 × 10 mL), the organic extracts were combined, dried over MgSO4 and evaporated to obtain compounds 26-30, 31a and 32. The 2-methyl-8-nitroquinazolin-4(3H)-one intermediate (31a) was reduced to compound 31 using the same procedure as reported in Scheme 1 for the synthesis of compounds 10, 16 and 22.General procedure: Compound 18 was prepared accordingto the procedure previously reported.39 A mixture of anthranilicacid 11 (0.1 mol) and formamide (18 g, 0.4 mol) was heated at130-135 C. After the mixture had been stirred for 4 h, water(40 mL) was added. The reaction mixture was cooled to 60 C, and water (20 mL) was added to the mixture. After the mixturehad been stirred for 30 min, the precipitated product wasfiltered off with suction. The crude products were recrystallizedwith ethanol to give compound 18 in yields of 80-95%.Examples 13 to 21:; The reaction and the post-treatment were carried out in the same manner as in Example 5, for which, however, the type of the anthranilic acid derivative was changed. The results are shown in Table 4.General procedure: A mixture of 2-aminobenzoic acid (0.1 mol) and formamide (20 mL)was refluxed for 10 h. After the mixture was cooled to room temperature, water (200 mL) was added and the precipitate was filtered off. Thecrude product was recrystallized from ethanol (100 mL) to the desiredintermediate 1 as a white solid.General procedure: 1 mmol of 2-iodo-5-methylbenzoic acid, 1 mmol of formamidine hydrochloride, and 8-quinolinolato copper (B ) 0.05 mmol, 1 mmol of sodium hydroxide and 3 mL of water. Placed in the microwave reactor, the microwave reactor at 150 W power heating 100 C to 30 minutes, cooled to room temperature. The product was extracted with ethyl acetate and concentrated under reduced pressure. The product was purified by column chromatography to give a white solid in 92% yield.General procedure: An excess of formamide (2 mL) solution containing each of the respective 2-aminobenzoic acids (1a-i) (1 mmol) was stirred at 120 C for 6 hours.After complete stirring, the resulting mixture was cooled and poured into ice cold water (10 mL). A 5% solution of NaHCO3 was gradually added to adjust the pH to 7, thereby forming a white solid.The solid was filtered and dried to give the quinazoline precursor 2, which was used in the next step without further purification.To a solution of acetone (4 mL) containing the quinazoline source 2K2CO3 (165.5 mg, 1.2 mmol) was added.The resulting mixture was stirred at 50 & lt; 0 & gt; C for 1 hour, A catalytic amount of KI (8.3 mg, 0.05 mmol) was added.After stirring for an additional 15 minutes, Methyl 4-bromobenzoate (1 mmol) was added.Until the reaction is terminated, The reaction mixture was stirred for another 5 h at 50 & lt; 0 & gt; C.The resulting mixture was evaporated under reduced pressure and redissolved in 50 ml of water to give a residue.The undissolved solid was filtered off and dried, And then redissolved in DMF (2 mL) to obtain an intermediate ester 3. After addition of hydroxylamine. HCI (685 mg, 10 mmol)A solution of NaOH (400 mg in 1 mL of water) was added dropwise.The mixture was stirred at room temperature until the reaction was complete (2-3 hours, confirmed by TLC). The resulting reaction mixture was poured into ice cold water, neutralized to pH ~ 7, and then acidified by dropwise addition of 5% HCl solution to induce maximum precipitation. The precipitate was filtered, dried, and recrystallized from methanol to obtain the desired compound 4.General procedure: Excess formamide (2 mL) solution containing each 2-aminobenzophosphoric acid (1a-i) (1 mmol) was stirred at 120 C. for 6 hours. After stirring was complete, the resulting mixture was cooled and poured into ice cold water (20 mL). NaHCO 35% solution was added gradually to adjust the pH to 8, thereby forming a white solid. The solid was filtered and dried to give quinazolineone derivative 2, which was used in the next step without further purification. To each solution of DMF (3 mL) containing quinazoline source 2 was added K 2 CO 3 (165.5 mg, 1.2 mmol). The resulting mixture was stirred for 30 min at 60 C., then a catalytic amount of KI (8.3 mg, 0.05 mmol) was added. After stirring for an additional 15 minutes, methyl 7-bromobenzoate or methyl 7-bromooctanoate (1 mmol) was added. The reaction mixture was stirred again at 60 C. for 3 hours until the reaction was complete. The resulting mixture was poured into 10 ml of water, neutralized with 5% HCl and extracted with DCM (3 × 15 mL). The organic layer was collected and filtered over anhydrous Na 2 SO 4. The solvent was removed under reduced pressure to yield intermediate esters 3, 4 as a yellow liquid. Each intermediate ester 3a-i, 4a-i was then dissolved in DMF and hydroxylamine.HCl (685 mg, 10 mmol) was added, followed by the dropwise addition of a solution of NaOH (400 mg in 1 mL of water). . Until the reaction was complete, the mixture was poured into ice cold water, neutralized to pH-7, and acidified by dropwise addition of 5% HCl solution to induce maximum precipitation. The precipitate was filtered, dried and recrystallized with methanol to give the desired compounds 5a-i, 6a-i.

Molecular Weight:180.59
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:180.0090405
Monoisotopic Mass:180.0090405
Topological Polar Surface Area:41.5
Heavy Atom Count:12
Complexity:229
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes