Carbonic acid-guanidine (1:1) → 1,2-Dihydroquinazoline

Temperature

150 °C

A mixture of 6-formyl-2-cyclopentyl-3-methoxycyclohex-2-en-1-one (2.0 g, 10.2 mmol) and guanidine carbonate (4.6 g) in DMF (30 mL) was heated at 150° C. for 4 hours. The solvent was removed under reduced pressure and to the residue ice-cold water was added. The product was extracted with ethyl acetate (3×50 mL). The combined organic extract was washed with water and brine and dried over anhydrous sodium sulfate. Solvent was removed under reduced pressure to give 2.0 g of crude dihydroquinazoline. The dihydroquinazoline was aromatized to the title compound by heating in nitrobenzene at 150° C. in the presence of 10% Pd-C. To a solution of dihydroquinazoline (2.0 g, 8.2 mmol) in nitrobenzene (20 mL), 200 mg of 10% Pd-C was added, and the reaction mixture was heated at 150° C. for 3 days. The Pd-C was removed by filtration. The filtrate was concentrated, and the resulting product was purified on a column of silica gel (Hex:EtOAc) to give the title compound as an off-white solid (1 g, 50% yield), mp 181–183° C.; 1H NMR (CDCl3): δ 1.6–2.2 (complex, 8H, 4×CH2), 3.9 (s, 3H, OCH3), 4.27 (t, 1H, CH), 5.02 (brs, 2H, NH2), 7.02 (d, 1H, Ar-H, J=9 Hz), 7.54 (d, 1H, Ar-H, J=9 Hz), 8.87 (s, 1H, Ar-H); MS m/z 244.07, C14H17N3O (M++1).

1. customThe solvent was removed under reduced pressure and to the residue ice-cold water
2. additionwas added
3. extractionThe product was extracted with ethyl acetate (3×50 mL)
4. extractionThe combined organic extract
5. washwas washed with water and brine
6. dry with materialdried over anhydrous sodium sulfate
7. customSolvent was removed under reduced pressure

ORD record

ord-ff832c0960ac477bbd6ce4df09b2f8f7

Source dataset

uspto-grants-2006_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06982260B1