N-Methyl-tert-butylamine → 8-bromo-2-(tert-butyl(methyl)amino)quinazolin-4(3H)-one
Reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9](Cl)[N:8]=[C:7]2[OH:13].[CH3:14][NH:15][C:16]([CH3:19])([CH3:18])[CH3:17]>CN1C(=O)CCC1>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([N:15]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH3:14])[NH:8][C:7]2=[O:13]Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 150 °C
Procedure
A mixture of 8-bromo-2-chloroquinazolin-4-ol (407c, 0.20 g, 0.77 mmol) in N-methyl-tert-butylamine (Aldrich; 0.919 mL, 7.71 mmol) and 1 mL NMP was sealed and heated to 150° C. in an oil bath for 6 h. The reaction was heated for 3 days. The reaction was partitioned between sat'd aq. NH4Cl and EtOAc. The organic layer was washed with sat'd aq. NH4Cl once, sat'd aq. NaCl once, and the organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The material was treated with 10% MeOH in DCM, adsorbed onto 1.5 g silica gel, and purified by silica gel chromatography (24 g column) using 0-50% EtOAc/hexanes. The product-containing fractions were concentrated to afford 8-bromo-2-(tert-butyl(methyl)amino)quinazolin-4(3H)-one (0.060 g, 0.19 mmol, 25% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.36 (1H, br. s.), 7.76-8.03 (2H, m), 6.95-7.14 (1H, m), 2.97 (3H, s), 1.55 (9H, s). m/z (ESI, +ve ion) 310.0/312.0 (M+H)+.