1-Methylpiperazine → HCID 58346467, compound

Participants

Reaction Steps

To 250 mL CH3CN were sequentially added 2-[6-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-4,5-dihydro-2H-pyrimido[5′,4′:4,5]thieno[2,3-e]indazol-2-yl]ethyl methanesulfonate (5.80 g, 9.67 mmol), 1-methylpiperazine (3.22 mL, 29.0 mmol), and diisopropylethylamine (3.37 mL, 19.3 mmol). The opaque white suspension was stirred with heating to reflux, upon which the contents turn brown and homogeneous. After 15 h the mixture was removed from heating, and allowed to cool to rt. The contents were concentrated under reduced pressure to 10% volume, diluted with CH2Cl2 (150 mL), and washed with aq NH4Cl (50 mL). The aqueous layer was separated and extracted with CH2Cl2 (50 mL), and the combined organic layers then washed with sat. NaHCO3 (2×100 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The solid product was triturated from methanol and then recrystallized from ethanol to afford the final product (3.22 g, 55%) as an off-white solid. 1H-NMR (CD2Cl2) δ 1.98 (s, 3H), 2.30-2.50 (broad m, 8H), 2.68 (t, 2H), 2.98 (t, 2H), 3.25 (t, 2H), 4.08 (t, 2H), 5.07 (s, 2H), 6.93-7.00 (m, 3H), 7.14-7.20 (m, 2H), 7.25-7.39 (m, 2H), 7.75 (s, 1H), 8.31 (s, 1H); LCMS RT=3.15 min; [M+H]+=604.3.

Provenance & Evidence