Hydrochloric Acid → N-{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-acetamide

Participants

Reaction Conditions

Reaction Steps

(2-Aminomethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine: A solution of 2-{4-[(4-methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-isoindole-1,3-dione (8.561 g, 20.2 mmol) in EtOH (100 mL) was treated with hydrazine mono-hydrate (3.0 mL, 61.8 mmol) and heated to 60° C. for 2 h. The reaction was cooled to rt, HCl (2 N, 50 mL) added and the reaction heated to 60° C. for 30 min. After cooling to rt the solid was filtered off. The filtrate was concentrated, basified with 5% NaOH and extracted with CH2Cl2. The organic layers were combined, dried (MgSO4), filtered and concentrated. The residue was purified by gradient reverse phase MPLC (MeCN/H2O with 0.1% TFA) and the free base re-extracted as above to yield 3.10 g (52%) of the title compound. 1H NMR (CDCl3) δ 7.76 (d, 1H), 7.54 (ddd, 1H), 7.08-7.16 (m, 2H), 6.95-7.05 (m, 2H), 6.86-6.94 (m, 2H), 4.07 (s, 2H), 3.84 (s, 3H), 3.60 (s, 3H), 2.00 (s(br), 2H); 13C NMR (CDCl3) δ 165.9, 162.0, 158.2, 152.2, 141.6, 132.0, 128.2, 127.6, 126.5, 124.4, 115.5, 115.4, 55.7, 49.1, 43.0; HRMS (ES) calcd for C17H18N4O (M+H) 295.1553, found 295.1506.

Provenance & Evidence