2,6-DIMETHYLQUINAZOLIN-4(3H)-ONE

General procedure: A two-neck round bottom flask was charged with a magnetic stirrer, evacuated and backfilled with nitrogen. Substituted 2-halobenzoic acid (1, 0.5 mmol) and amidine hydrochloride (2, 0.75 mmol) or bis(guanidine) sulphate (2, 0.38 mmol) in 2 wt percent TPGS-750-M (3 mL) were added under nitrogen atmosphere. After a 10-min stirring, Cs2CO3 (1 mmol, 326 mg) was added to the flask. 15 min later, CuI (0.1 mmol, 19 mg) was added to the flask. The mixture was allowed to stir under nitrogen atmosphere at the shown temperature for 12 h (see Table 3 in text). After completion of the reaction, the mixture was extracted with EtOAc (1 mL), and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using petroleum ether/ethyl acetate (3:1 to 1:1) as eluent to provide the desired product.General procedure: N -(2-aminobenzoyl)benzotriazoles (0.25 mmol) 1 previously synthesized by our group were reacted with orthoester (0.50 mmol) 2 and ammonium acetate (1.0 mmol) in dioxane for 6-10 h. After completion of the reaction, the solvent was evaporated under reduced pressure. The reaction mixture was purified by column chromatography over silica gel with a EtOAc/n-hexane mixture (from 1:2 or 1:1) to obtain white crystals (62%-95%).General procedure: 2-Amino-3-naphthoic acid or 2-amino-3-benzoic acid (1 eq) was dissolved in acetic anhydride (0.2 M final) and heated to reflux. After stirring a reflux for 4 h, reaction mixture was cooled to room temperature and solvent was removed by rotary evaporator. Concentrated NH4OH (0.2 M final) was added to residue and the solution was heated at 100 C for 12 h. Once cooled to room temperature, the resulting precipitate was collected by filtration and washed with H20 and methanol yielding a solid (1.72 g, 72%). 'H and 13C NMR were consistent with previous reports.General procedure: Each mixture of 2-aminobenzoic acid (1a-c) (2 mmol) and acetic anhydride (2 mL) was heated to reflux (120 C.) until the reaction was complete (1-2 hours). Then ammonium acetate (308 mg, 4 mmol) was added. The reaction mixture was stirred again at 80 C. for 3 hours. At the end of the reaction, the resulting mixture was cooled and poured into ice cold water. The precipitate was filtered and dried to give 2-methylquinazolin-4 (3H) -one derivative 7 which was used in the next step without further purification. To each solution of DMF (3 mL) containing compound 8a-c (1 mmol) was added K 2 CO 3 (165.5 mg, 1.2 mmol). The resulting mixture was stirred for 30 min at 60 C., then KI (8.3 mg, 0.05 mmol) was added. After stirring for an additional 15 minutes, 0.5 ml solution of DMF containing methyl 7-bromoheptanoate was slowly added dropwise to the mixture. The reaction mixture was stirred again at 60 C. for 3 hours. The reaction mixture was then poured into ice cold water (10 mL). A precipitate was obtained, washed with water and dried to give a compound (of intermediate 9a-c above). Each ester intermediate 9a-c was dissolved in DMF and hydroxylamine hydrochloride (685 mg, 10 mmol) was added and then added dropwise to a solution of NaOH (400 mg in 1 mL water). The mixture was stirred for 30 min at -5 C. At the end of the reaction, the resulting mixture was poured into ice cold water, neutralized to pH-7 and slightly acidified by dropwise addition of 5% HCl solution to induce maximum precipitation. The precipitate was filtered off, dried and recrystallized in methanol to yield the title compound 10a-c.

Molecular Weight:174.20
XLogP3:1.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:174.079312947
Monoisotopic Mass:174.079312947
Topological Polar Surface Area:41.5
Heavy Atom Count:13
Complexity:260
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes