반응 #303357

ord-fa9a37255da2416ba307759acfcddf78

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    추출extracted with ethyl acetate
  2. 2
    건조The extracts are dried (MgSO4)
  3. 3
    여과filtered
  4. 4
    농축concentrated
  5. 5
    기타chromatographed (SiO2, 40% EtOAc in Heptane)
  6. 6
    기타to afford
  7. 7
    농축the mixture is concentrated
  8. 8
    기타triturated (ether)
  9. 9
    여과filtered

실험 절차

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

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08193183B2uspto-grants-2012_06