Journal of Medicinal Chemistry Table 9. continued Article Example 25 was obtained from 13a by a Pd2(dba)3 mediated amination reaction with 4-ﬂuoroaniline followed by a TFA mediated deprotection by analogy to compound 22 (55% yield over 2 steps). 1H NMR (400 MHz, DMSO-d6): δ 8.06 (m, 2H), 7.98 (m, 1H), 7.80 (m, 2H), 7.16 (m, 2H), 6.98 (m, 2H), 6.60 (m, 2H), 4.64 (m, 2H), 4.02 (m, 2H), 3.80 (m, 2H), 1.38 (s, 6H). m/z = 412.1 (M + 1). Synthesis of 7b. 2-(4-Fluorophenyl)-7-(4-methoxybenzyl)-5,5- dimethyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine: Compound 7b was prepared from compound 7a (R1 = R2 = H) by the following way: To a solution of compound 7a (231 mg, 1.0 mmol) in DMF (10 mL) were added KOH (168 mg, 3.0 mmol) and PMBCl (405 μL, 3.0 mmol) at 0 °C. The reaction mixture was stirred at the same temperature for 2 h and at rt for 2 additional hours. The reaction mixture was puriﬁed by reverse phase HPLC. The HPLC fraction were evaporated under reduced pressure and neutralized by satd NaHCO3. The compound was extracted by ethyl acetate and dried over sodium sulfate. The organic layer was concentrated under reduced pressure to give compound 7a-1 (221 mg, 63%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.67−7.63 (m, 2H), 7.28− 7.25 (m, 2H), 7.07−7.02 (m, 2H), 6.89−6.86 (m, 2H), 4.74 (s, 2H), 4.70 (m, 2H), 4.53 (s, 2H), 3.79 (s, 3H). To a solution of compound 7a-1 (253 mg, 0.72 mmol) in DMF (15 mL) were added 60% sodium hydride (87 mg, 0.085 mmol) and methyl iodide (0.45 mL, 7.2 mmol) at rt. The reaction mixture was stirred at rt for 2 h. The reaction mixture was quenched with methanol and directly subjected to mass-triggered HPLC puriﬁcation to give 7a-2 as a white solid after evaporation of 4264 dx.doi.org/10.1021/jm300041e | J. Med. Chem. 2012, 55, 4244−4273