2-amino-N-(furan-2-ylmethyl)benzamide

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-(chloromethyl)-4-methoxybenzaldehyde (91.0 mg, 0.5 mmol, 1.0 equiv) and 2,6-dimethylbenzenethiol (68.4 mg, 0.5 mmol, 1.0 equiv) in 4 mL acetonitrile was added potassium carbonate (0.55 g, 4.0 mmol, 8.0 equiv). The mixture was heated to 150° C. in the microwave for 10 min. After filtered off the solid and removed the solvent, 2-amino-N-(furan-2-ylmethyl)benzamide (107 mg, 0.5 mmol, 1.0 equiv) in 5 mL of EtOH was added followed by addition of Ytterbium trifluoromethanesulfonate (62 mg, 0.1 mmol, 0.2 equiv). The mixture was heated at 80° C. for 2 hours. Upon completion, the mixture was dried down and chromatographed on silica gel with 10-60% EtOAc/Hexanes gradient elution to give 2-(3-((2,6-dimethylphenylthio)methyl)-4-methoxyphenyl)-3-(furan-2-ylmethyl)-2,3-dihydroquinazolin-4(1H)-one (101.4 mg, 42%) as a white solid after triturating with diethyl ether. 1HNMR (400 MHz, DMSO-d6) δ ppm 2.26 (s, 6 H), 3.56 (d, J=15.7 Hz, 1 H), 3.66 (s, 3 H), 3.72 (d, 1 H), 3.79 (d, 1 H), 5.12 (d, J=15.7 Hz, 1 H), 5.55 (d, J=2.2 Hz, 1 H), 6.25 (d, J=3.1 Hz, 1 H), 6.41 (dd, J=3.0, 1.9 Hz, 1 H), 6.59 (d, J=8.0 Hz, 1 H), 6.66 (t, J=7.5 Hz, 1 H), 6.78-6.94 (m, 2 H), 7.00-7.28 (m, 6 H), 7.59-7.66 (m, 2 H); LCMS: (electrospray+ve), m/z 485.2 (MH)+, tR=7.16 min, UV254=98%. HRMS (ESI): m/z calcd for C29H28N2O3S [M+H]+485.1905, found 485.1905. After filtered off the solid was added The mixture was heated at 80° C. for 2 hours Upon completion, the mixture was dried down chromatographed on silica gel with 10-60% EtOAc/Hexanes gradient elution

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-(chloromethyl)-4-methoxybenzaldehyde (85 mg, 0.46 mmol, 1.0 equiv) and 2,6-dimethylphenol (62 mg, 0.51 mmol, 1.1 equiv) in 3.0 mL of anhydrous acetonitrile, we added K2CO3 (320 mg, 2.3 mmol, 5.0 eq). The mixture was heated in a microwave reactor for 30 min at 150° C. After filtering off the solid and removing the solvent, 2-amino-N-(furan-2-ylmethyl)benzamide (110 mg, 0.51 umol, 1.1 equiv) in 5 mL of EtOH was added followed by addition of Ytterbium trifluoromethanesulfonate (57 mg, 0.02 umol, 0.2 equiv). The mixture was heated at 80° C. for 2 hours. The product was isolated via preparative HPLC purification and solvent was removed via reduced pressure lyophilization to give 2434(2,6-dimethylphenoxy)methyl)-4-methoxyphenyl)-3-(furan-2-ylmethyl)-2,3-dihydroquinazolin-4(1H)-one (64.5 mg, 30%) as a white solid after triturating with diethyl ether. 1HNMR (400 MHz, DMSO-d6) δ ppm 2.16 (s, 6H), 3.77 (s, 3 H), 3.86 (d, J=15.6 Hz, 1 H), 4.69 (d, J=1.9 Hz, 2 H), 5.19 (d, J=15.4 Hz, 1 H), 5.75 (d, J=2.3, Hz, 1 H), 6.30 (d, J=3.2 Hz, 1 H), 6.39 (dd, J=3.2, 1.9 Hz, 1 H), 6.62-6.70 (m, 2 H), 6.86-6.97 (m, 1 H), 6.99-7.04 (m, 3 H), 7.19-7.29 (m, 2 H), 7.32 (d, J=2.3 Hz, 1 H), 7.49 (d, J=2.4, Hz, 1 H), 7.57 (dd, J=1.8, 0.7 Hz, 1 H), 7.68 (dd, J=7.9, 1.5 Hz, 1 H); HPLC: tR=6.88 min, UV254=97%; HRMS (ESI): m/z calculated for C29H28N2O4 [M+1]+469.2132, found 469.2138. After filtering off the solid was added The mixture was heated at 80° C. for 2 hours The product was isolated via preparative HPLC purification and solvent was removed via reduced pressure lyophilization