반응 #88788

ord-0c593c27c4b24b1eaad4ecdbeff8abe7

용매

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도The reaction was heated at 140° C. (MW) for 2 h
  2. 2
    세척The organic layer was washed with water (20 mL) and brine (20 mL)
  3. 3
    건조dried over Na2SO4
  4. 4
    농축concentrated to a residue which
  5. 5
    기타was purified by chromatography
  6. 6
    세척eluted with PE/EA (10:1 to 1:1)

실험 절차

To a mixture of 6-bromo-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 20, step 4, 200 mg, 0.50 mmol), CuI (28.7 mg, 0.15 mmol), Cs2CO3 (327.2 mg, 1.00 mmol) and 2-(dimethylamino)acetic acid (10.4 mg, 0.10 mmol) in dioxane (3 mL) was added 3-(trifluoromethyl)phenol (162.8 mg, 1.00 mmol). The reaction was heated at 140° C. (MW) for 2 h, cooled to RT then diluted with EA (15 mL) and water (10 mL). The organic layer was washed with water (20 mL) and brine (20 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (10:1 to 1:1) to give 1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoromethyl)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (150 mg, 62.3% yield) as a white solid. LCMS: [MH+-THP] 396 and TR=1.941 min.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US09440972B2uspto-grants-2016_09