Reaction Steps
[5-(1-(2-Fluorobenzenesulfonyl)piperidin-4-ylmethoxy]quinazoline-2,4-diamine (Method CC) (Example-025). To a mixture of 5-(piperidin-4-ylmethoxy)quinazoline-2,4-diamine (250 mg; 0.9 mmol) and triethylamine (0.3 mL; 1.8 mmol) in 2.5 mL N,N-dimethylformamide was added 2-fluorobenzenesulfonyl chloride (196 mg; 1.0 mmol) and stirred at room temperature for 5 hours. Reaction was quenched with 1 mL 1N NaOH creating a homogenous mixture. After 1.5 hours, 1 mL of water was added to the newly formed precipitates and solids were collected by filtration. Solids were triturated with ethanol and rinsed once with diethyl ether to yield crude compound. (331 mg; 85% yield). 5-[1-(2-Fluorobenzenesulfonyl)piperidin-4-ylmethoxy]quinazoline-2,4-diamine (250 mg, 0.6 mmol) was purified by silica gel column (5% MeOH/CH2Cl2+1% NH4OH). The fractions were reduced to 5 mL and diluted with 2 M HCl in Et2O (5 mL). The solvents were completely removed under N2 purge. The resulting semi-solid was triturated with absolute EtOH, and stored at 2° C. for 72 hours. The resulting solids are filtered and dried under vacuum at 30° C. overnight to yield 182 mg of 5-[1-(2-fluorobenzenesulfonyl)piperidin-4-ylmethoxy]quinazoline-2,4-diamine hydrochloride. 1HNMR (500 MHz, DMSO-d6) δ 12.93 (s, 1H), 8.95 (s, 1H), 8.16 (s, 1H), 7.80 (t, J=7.5 Hz, 1H), 7.77 (dt, J=7.5, 2.5 Hz, 1H), 7.68 (t, J=8.5 Hz, 1H), 7.50 (t, J=8.5 Hz, 1H), 7.45 (t, J=7.5 Hz, 1H), 6.99 (d, J=8.5 Hz, 1H), 4.14 (d, J=6.5 Hz, 2H), 3.74 (br d, J=12.0 Hz, 2H), 2.54 (m, 2H), 2.07 (m, 1H), 1.84 (br d, J=12 Hz, 2H), 1.33 (m. 2H). 12CNMR (500 MHz, DMSO-d6) δ 162.3, 159.2, 157.2, 156.8, 154.2, 141.0, 136.2, 135.8, 130.8, 125.1, 124.2, 117.6, 117.5, 108.6, 106.8, 99.6, 73.1, 45.1, 33.4, 27.8. MS m/z (ESI) 432 (M+H)+.
