反应详情

A mixture of 2-fluoro-5-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzaldehyde [275 mg, 072 mmol, Example 35(j)], unsym-dimethylethylenediamine (217 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 water with (50 mL) and the aqueous 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 7% MeOH in DCM gradient to afford a solid that is dissolved in methanol. This solution is treated with hydrogen chloride in EtOAc and concentrated to afford N-(2-fluoro-5-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzyl)-N′,N′-dimethyl-ethane-1,2-diamine hydrochloride [300 mg, 92%, Example 13(d)]. LCMS: RT=2.04 minutes, MS: 454 (M+H). IC50=56 nM

1. filtrationThe reaction mixture is filtered
2. washthe filter cake is washed with DCM (50 mL)
3. extractionThe combined filtrate and washings are extracted water with (50 mL)
4. extractionthe aqueous is extracted with DCM (50 mL)
5. extractionThe new organic extract
6. washis washed with water (30 mL), with brine (30 mL)
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated by rotary evaporator
10. washeluting with 0 to 7% MeOH in DCM gradient
11. customto afford a solid
12. concentrationconcentrated