تفاعل #303357
ord-fa9a37255da2416ba307759acfcddf78
معادلة التفاعل
المتفاعلات
الكواشف
ظروف التفاعل
المعالجة
- 1استخلاصextracted with ethyl acetate
- 2تجفيفThe extracts are dried (MgSO4)
- 3ترشيحfiltered
- 4تركيزconcentrated
- 5أخرىchromatographed (SiO2, 40% EtOAc in Heptane)
- 6أخرىto afford
- 7تركيزthe mixture is concentrated
- 8أخرىtriturated (ether)
- 9ترشيحfiltered
الإجراء التجريبي
To a suspension of (2-Methoxy-phenyl)-methanol (860 mg, 6.22 mmol), and sodium hydride (60%, 0.3 g) in DMF (10 mL) is add (6-Chloro-2-methoxy-pyrimidin-4-yl)-[2-(4-methoxy-phenyl)-ethyl]-amine [0.54 g, 1.8 mmol, Intermediate (8)] at 10° C. After 1 h at 60° C., the mixture is diluted with H2O, and extracted with ethyl acetate. The extracts are dried (MgSO4), filtered, concentrated, and chromatographed (SiO2, 40% EtOAc in Heptane) to afford a non-separable mix of the product, [2-Methoxy-6-(2-methoxy-benzyloxy)-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine, and the disubstituted side product, [2,6-Bis-(2-methoxy-benzyloxy)-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine. To above mixture in CH2Cl2 is added a solution of HCl in EtOAc, and the mixture is concentrated, triturated (ether), and filtered to give 141 mg (19%) of 4-(2-Methoxy-benzyloxy)-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-2-ol hydrochloride as a solid. LCMS: RT=2.07 minutes, MS: 382 (M+H). The filtrate is concentrated, and chromatographed (silica gel, 40% EtOAc in Heptane) to afford [2-Methoxy-6-(2-methoxy-benzyloxy)-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine hydrochloride [39 mg, 5%, Example (48)] as an oil. LCMS: RT=3.3 minutes, MS: 396 (M+H). IC50=12 nM