N,N,N',N'-Tetramethylethylenediamine → (E)-4-(4-chlorostyryl)-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-2(1H)-one

Participants

Reaction Steps

To a stirred mixture of (E)-4-(4-chlorostyryl)pyrimidin-2(1H)-one Part A (21 mg, 0.09 mmol), 4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenylboronic acid Part D of Procedure 4 (43 mg, 0.18 mmol) and copper (II) acetate (16.39 mg, 0.090 mmol) in MeOH (2 mL) and H2O (0.5 mL) was added N1,N1,N2,N2-tetramethylethane-1,2-diamine (21 mg, 0.18 mmol) at RT. After stirring at RT for 45 min under oxygen, the reaction diluted with CH2Cl2 and washed sequentially with 5% aq. sulfuric acid and sat. NaHCO3. The organic phase was dried (MgSO4) and concentrated. LC/MS showed incomplete reaction (starting pyrimidinone:desired product=ca. 4:1). The crude product mixture was resubjected to the above reaction conditions using another 2 equivalents of the boronic acid, copper salt and N1,N1,N2,N2-tetramethylethane-1,2-diamine After the above described workup, the crude product mixture was subjected to preparative HPLC (ODS column/water-MeOH-TFA 90:10:0.1 to 10:90:0.1 gradient) to afford a brown solid. Further purification was achieved by dissolution of this solid in a few drops of MeOH followed by addition of MTBE (ca. 1 mL) which upon standing at RT induced the formation of a yellow precipitate. The precipitated yellow solid was isolated to afford the title compound (E)-4-(4-chlorostyryl)-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-2(1H)-one B-6 (8 mg, 0.018 mmol, 20% yield) as a yellow solid. LC/MS 427 (M+H)+, tR 0.84 min (method 5); 1H NMR (400 MHz, chloroform-D) δ 7.91 (1H, d, J=16.06 Hz), 7.69 (1H, d, J=6.78 Hz), 7.54 (2H, d, J=8.28 Hz), 7.39 (2H, d, J=8.53 Hz), 6.87-7.01 (4H, m), 6.49 (1H, d, J=6.78 Hz), 3.87 (3H, s), 3.85 (2H, s), 1.36 (6H, s).

Provenance & Evidence