Hydrochloric Acid → (6-{4-Fluoro-3-[(2-methoxy-ethylamino)-methyl]-phenyl}-2-methoxy-pyrimidin-4-yl)-[2-(4-methoxy-phenyl)-ethyl]-amine hydrochloride

Participants

Reaction Steps

A mixture of 2-fluoro-5-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzaldehyde [300 mg, 0.787 mmol, Example 35(j)], 2-methoxyethylamine (170 μL, 1.97 mmol), sodium triacetoxyborohydride (500 mg, 2.36 mmol) and 3 Å sieves (500 mg) in DCM (7 mL) is stirred at room temperature under a nitrogen atmosphere for 5 hours. The reaction mixture is filtered and the filter cake is washed with DCM (50 mL). The combined filtrate and washings are extracted with water (50 mL). The aqueous extract is extracted with DCM (50 mL). The new organic extract is washed with water (30 mL), with brine (30 mL), dried over sodium sulfate, filtered and concentrated by rotary evaporator. The resulting solid is subjected to flash column chromatography on silica (4.5 g) eluting with 0 to 8% MeOH in DCM gradient to afford a solid. This material is treated with hydrogen chloride in EtOAc and concentrated to afford (6-{4-fluoro-3-[(2-methoxy-ethylamino)-methyl]-phenyl}-2-methoxy-pyrimidin-4-yl)-[2-(4-methoxy-phenyl)-ethyl]-amine hydrochloride [260 mg, 75%, Example 13(b)] as a solid. LCMS: RT=1.98 minutes, MS: 441 (M+H). 1H NMR (300 MHz, CDCl3): δ 9.65 (1H, s), 8.27 (1H, s), 7.91 (1H, s), 7.47 (1H, t, J=0.03 Hz), 7.21 (2H, d, J=0.027 Hz), 6.85 (2H, d, J=0.027 Hz), 4.26 (2H, s), 4.03 (2H, s), 3.72 (6H, s), 3.31 (3H, s), 3.17 (2H, m), 2 (2H, t, J=0.024), 2.5 (2H, s).

Provenance & Evidence