N,N-Dimethylglycine → 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

HRID 60510노트

반응식

HRID 60510 반응식
[Si]([O:8][CH2:9][CH2:10][CH2:11][N:12]1[C:17](=[O:18])[C:16]2[C:19](C(C3C=CC(Cl)=CC=3)O)=[C:20](C3C=CC=CC=3C(C)C)[CH:21]=[N:22][C:15]=2[N:14]([CH3:41])[C:13]1=[O:42])(C(C)(C)C)(C)C.[C:43]([O-])([O-])=O.[Cs+].[Cs+].CN(C)CC(O)=O.[F:56][C:57]([F:66])([F:65])[C:58]1[CH:59]=[C:60]([OH:64])[CH:61]=[CH:62][CH:63]=1.O1[CH2:72][CH2:71][O:70][CH2:69][CH2:68]1>CC(=O)OCC.O.[Cu]I>[CH3:41][N:14]1[C:15]2[N:22]=[CH:21][C:20]([O:64][C:60]3[CH:61]=[CH:62][CH:63]=[C:58]([C:57]([F:65])([F:66])[F:56])[CH:59]=3)=[CH:19][C:16]=2[C:17](=[O:18])[N:12]([CH2:11][CH2:10][CH2:9][O:8][CH:71]2[CH2:72][CH2:43][CH2:68][CH2:69][O:70]2)[C:13]1=[O:42]

참가 물질

9

반응물 5

HCID 673N,N-DimethylglycineHCID 73763-(Trifluoromethyl)phenolHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 1317370933-(3-((tert-butyldimethylsilyl)oxy)propyl)-5-((4-chlorophenyl) (hydroxy)methyl)-6-(2-isopropylphenyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione2회

생성물 1

HCID 1188755091-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoromethyl) phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione수율 62.3%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 962Water용매HCID 8857Ethyl Acetate용매

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.

후처리

  1. temperatureThe reaction was heated at 140° C. (MW) for 2 h
  2. washThe organic layer was washed with water (20 mL) and brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to a residue which
  5. customwas purified by chromatography
  6. washeluted with PE/EA (10:1 to 1:1)

출처 및 근거

ORD 기록
ord-0c593c27c4b24b1eaad4ecdbeff8abe7
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440972B2

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