N,N-Dimethylglycine → 1-methyl-6-((6-methylpyridin-3-yl)oxy)-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60434

반응식

HRID 60434 반응식
[OH:1][C:2]1[CH:24]=[N:23][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[C:9](=[O:10])[C:4]=2[CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].CN(C)CC(O)=O.Br[C:39]1[CH:40]=[CH:41][C:42]([CH3:45])=[N:43][CH:44]=1>O1CCOCC1.CC(=O)OCC.O.[Cu]I>[CH3:22][N:6]1[C:5]2[N:23]=[CH:24][C:2]([O:1][C:39]3[CH:44]=[N:43][C:42]([CH3:45])=[CH:41][CH:40]=3)=[CH:3][C:4]=2[C:9](=[O:10])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][O:16]2)[C:7]1=[O:21]

참가 물질

9

반응물 4

HCID 673N,N-DimethylglycineHCID 10796Cesium carbonateHCID 12010205-Bromo-2-methylpyridineHCID 1188754886-hydroxy-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione2회

생성물 1

HCID 1188754911-methyl-6-((6-methylpyridin-3-yl)oxy)-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione수율 77.1%

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

반응 조건

온도
135 °C

실험 절차

To a suspension of 6-hydroxy-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 36, step 2, 500 mg, 1.49 mmol), CuI (85.2 mg, 0.45 mmol), Cs2CO3 (971.6 mg, 2.98 mmol) and 2-(dimethylamino)acetic acid (76.87 mg, 0.75 mmol) in dioxane (20 mL) was added 5-bromo-2-methylpyridine (641.2 mg, 3.73 mmol). The reaction was heated at 135° C. for 5 h followed by heating at 100° C. for 18 h, cooled to RT then diluted with EA (25 mL) and water (10 mL). The organic layer was washed with water (20 mL) and brine (20 mL), dried over Na2SO4 and concentrated to residue which was purified by chromatography eluted with PE/EA (5:1 to 1:1) to give 1-methyl-6-((6-methylpyridin-3-yl)oxy)-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (490 mg, 77.1% yield) as a yellow oil. LCMS: [MH+-THP] 343 and TR=1.215 min.

후처리

  1. temperatureby heating at 100° C. for 18 h
  2. temperaturecooled to RT
  3. washThe organic layer was washed with water (20 mL) and brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to residue which
  6. customwas purified by chromatography
  7. washeluted with PE/EA (5:1 to 1:1)

출처 및 근거

ORD 기록
ord-ed7c926a58c44646a09673d434021e88
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440972B2

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