2-amino-N-(2-methoxyethyl)benzamide

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

Procedure: 2-amino-N-(2-methoxyethyl)benzamide (71.2 mg, 0.367 mmol), N-(4-(5-formyl-2-methoxybenzyloxy)-3,5-dimethylphenyl)acetamide (100 mg, 0.305 mmol) and 0.2 equiv of Yb(OTf)3 in 5 mL of EtOH were heated at 80° C. for 2 h. The reaction mixture was concentrated under reduced pressure and the residue was chromatographed on silica-gel using 10-80% ethyl acetate in DCM to give the N-(4-(2-methoxy-5-(3-(2-methoxyethyl)-4-oxo-1,2,3,4-tetrahydroquinazolin-2-yl)benzyloxy)-3,5-dimethylphenyl)acetamide (77.9 mg, 0.155 mmol, 50.6% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.97 (s, 3 H), 2.09 (s, 6 H), 2.90 (ddd, J=13.5, 6.7, 6.5 Hz, 1 H), 3.19 (s, 3 H), 3.31-3.53 (m, 2 H), 3.74 (s, 3 H), 3.86-4.06 (m, 1 H), 4.63 (s, 2 H), 5.85 (d, J=2.3 Hz, 1 H), 6.53-6.69 (m, 2 H), 6.98 (d, J=8.6 Hz, 1 H), 7.12-7.22 (m, 3 H), 7.22-7.31 (m, 2 H), 7.47 (d, J=2.3 Hz, 1 H), 7.61 (d, J=6.7 Hz, 1 H), 9.67 (s, 1 H); LC/MS (electrospray+ve), m/z 504.2 (MH)+, Retention time t=5.27 min; Purity: UV220>98%, UV254>98%; HRMS (ESI): m/z calcd for C29H33N3O5 [M+H]+504.2496, found 504.2498. The reaction mixture was concentrated under reduced pressure the residue was chromatographed on silica-gel