Guanidine Hydrochloride → 2-amino-7-(3-(6-methoxypyridin-2-yl)thiophen-2-yl)-4-methyl-7,8-dihydroquinazolin-5(6H)-one

Participants

Reaction Conditions

Reaction Steps

To a 150 mL pressure vessel was added 2-acetyl-3-hydroxy-5-(3-(6-methoxypyridin-2-yl)thiophen-2-yl)cyclohex-2-enone (30G, 1.72 g, 5.01 mmol, 1.0 eq.), EtOH (50 mL), pyrrolidine (2.13 g, 30.1 mmol, 6.0 eq.), guanidine hydrochloride (1.44 g, 15 mmol, 3.0 eq.). The vessel was sealed and heated overnight at 100° C. LC/MS analysis showed the reaction to be complete whereupon the reaction mixture was concentrated and the residue was taken up in 20% EtOAc/CH2Cl2. An insoluble solid proving not to be product was filtered off. The remaining filtrate was purified via column chromatography (20% EtOAc/CH2Cl2 to 70% EtOAc/CH2Cl2) to yield the product 30H as a light gray solid (270 mg, 15%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.55 (s, 3H) 2.76-2.95 (m, 2H) 3.02-3.22 (m, 2H) 3.70 (s, 3H) 4.62-4.77 (m, 1H) 6.72 (d, J=8.34 Hz, 1H) 7.31 (d, J=7.58 Hz, 1H) 7.41-7.54 (m, 4H) 7.75 (t, J=7.83 Hz, 1H). ESI-MS: m/z 367.3 (M+H)+.

Provenance & Evidence