Stannous chloride dihydrate → HCID 136347863, compound

Temperature

0 °C

To a stirred suspension of 7-aminoquinazolin-4-ol (2.00 g, 12.4 mmol) in conc. HCl (20.0 ml) at 0° C. was added dropwise NaNO2 (0.98 g, 14.3 mmol, 1.15 eq) as a solution in H2O (15.0 ml). The resulting mixture was stirred at 0° C. for 1 h, and then treated with a solution of SnCl2.2H2O (12.0 g, 53.4 mmol, 4.30 eq) in conc. HCl (15.0 ml). The reaction was stirred at 0° C. for 1 h and then at RT for 2 h. The reaction was diluted with EtOH (130 ml) and 4,4-dimethyl-3-oxopentanenitrile (2.02 g, 16.1 mmol, 1.30 eq) added, heated at reflux overnight, then cooled to RT and concentrated. The residue was diluted with EtOAc (100 mL), placed in an ice/H2O bath and the stirred solution made basic (pH 8) with solid NaOH. The mixture was filtered through Celite®, washed with H2O (50 mL) and then EtOAc (100 mL). The organic phase washed with brine, dried (Na2SO4) and concentrated to yield a tan solid, which was dried then stirred in ether (100 mL) and allowed to stand. The solid was collected by filtration and dried to yield 7-(5-amino-3-t-butyl-1H-pyrazol-1-yl)quinazolin-4(3H)-one (1.69 g, 48% yield). 1H NMR (300 MHz, DMSO-d6): 8.17-8.11 (m, 2H), 7.90-7.83 (m, 2H), 5.47 (m, 3H), 1.23 (s, 9H). MS (ESI) m/e (M+H+) 284.2.

1. stirringThe reaction was stirred at 0° C. for 1 h
2. waitat RT for 2 h
3. additionadded
4. temperatureheated
5. temperatureat reflux overnight
6. temperaturecooled to RT
7. concentrationconcentrated
8. additionThe residue was diluted with EtOAc (100 mL)
9. customplaced in an ice/H2O bath
10. filtrationThe mixture was filtered through Celite®
11. washwashed with H2O (50 mL)
12. washThe organic phase washed with brine
13. dry with materialdried (Na2SO4)
14. concentrationconcentrated
15. customto yield a tan solid, which
16. customwas dried
17. stirringthen stirred in ether (100 mL)
18. filtrationThe solid was collected by filtration
19. customdried

ORD record

ord-82d9be44ac53482bba901846fe10a05b

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08163756B2