Reaction Steps
A solution of 10 (0.835 g, 2.43 mmol) and aniline hydrochloride (0.47 g, 3.64 mmol) in absolute EtOH (10 mL) was refluxed for 1 h. In a separate flask, guanidine hydrochloride (1.09 g, 11.4 mmol) was added to a solution of NaOEt prepared by dissolving clean metallic Na (345 mg, 15 mmol) in absolute EtOH (15 mL) and the flask was swirled manually for 5 min. The entire contents of the second flask (including the NaCl) were added to the first, and the combined mixture was refluxed for 18 h and then filtered while hot. TLC analysis of the filtrate (silica gel, 10:1 EtOAc-MeOH) showed the product (3a) as a major UV-absorbing spot (Rf0.3), along with several fast-moving impurities. Flash chromatography (silica gel, 18 g, 2×15 cm) with 10:1 EtOAc-MeOH as the eluent afforded an amorphous solid, which on recrystallization from aqueous EtOH afforded 3a as white flakes (540 mg, 70%); mp 140–141° C.; IR (KBr) ν 3410, 3330, 3230, 3120, 2990, 2950, 2910sh, 2870, 2830, 1665, 1635, 1605, 1565, 1540, 1505, 1480, 1460, 1440, 1420 cm−1; 1H NMR (200 MHz, DMSO-d6) δ 0.87 (m, 3H, pentyl Me), 1.33 (m, 4H, pentyl 3- and 4-CH2), 1.64 (p, J=7 Hz, 2H, pentyl 2-CH2), 3.47 (s, 2H, bridge CH2), 3.73 (s, 3H, OMe), 3.83 (t, J=7 Hz, 2H, OCH2), 5.65 (broad s, 2H, NH2), 6.02 (br s, 2H, NH2), 6.64 (d, J=3 Hz, 1H, aryl H-6), 6.70 (dd, J=8 Hz, J=3H, 1H, aryl H-4), 6.87 (d, J=8 Hz, 1H, aryl H-3), 7.39 (s, 1H, pyrimidine H-6).
