2,2'-Oxybisacetaldehyde → 7-methoxy-3-(4-methoxyphenyl)-4-morpholinoisoquinolin-1(2H)-one

Participants

Reaction Steps

NaIO4 (66 mg, 0.33 mmol) is added to a flask containing 1,4-anhydroerythritol (34 mg, 0.33 mmol) dissolved in a water/CH3CN mixture (1:1; 4 mL) and the mixture is maintained under stirring for 18 hours. 4-amino-7-methoxy-3-(4-methoxyphenyl)isoquinolin-1(2H)-one (compound 1) (100 mg, 0.33 mmol) and NaBH3CN (63 mg, 1 mmol) are then added to the solution of 2,2′-oxybis(acetaldehyde) prepared previously. Then, 3 drops of acetic acid are added and the medium is stirred for 3 hours at ambient temperature. The reaction is stopped by the addition of 10 mL of water. The medium is extracted with 3×10 mL of dichloromethane. The organic phases are washed with 3×10 mL of water, dried over MgSO4 and concentrated under vacuum. The residue is purified by silica gel column chromatography with dichloromethane-ethanol (100/0 to 98/2) as eluent in order to produce successively i) the compound 7-methoxy-3-(4-methoxyphenyl)-4-morpholinoisoquinolin-1(2H)-one 49 (10 mg, 8%) in the form of a white solid, mp>270° C.; 1H NMR (CDCl3): 8.18 (1H, br s), 7.99 (1H, d), 7.83 (1H, dd), 7.37 (3H, m), 7.03 (2H, d), 3.97 (3H, s), 3.91 (3H, s), 3.72 (4H, m), 2.90 (2H, m), 2.75 (2H, m); MS 367 (M+H); and ii) the compound 4-(2-(2-hydroxyethoxy)ethylamino)-7-methoxy-3-(4-methoxyphenyl)isoquinolin-1(2H)-one 50 (15 mg, 12%) in the form of a white solid, mp 139° C.; 1H NMR (CDCl3): 8.71 (1H, br s), 7.89 (1H, d), 7.82 (1H, s), 7.45 (2H, d), 7.34 (1H, dd), 7.01 (2H, d), 3.94 (3H, s), 3.87 (3H, s), 3.60 (2H, t), 3.49 (2H, t), 3.38 (2H, t), 3.03 (2H, t), 1.75 (1H, br s), MS 385 (M+H).

Provenance & Evidence