N,N-Dimethylglycine → 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-(3-chlorophenoxy)-1-methyl pyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

HRID 60168

Reaktionsgleichung

Reaktionsgleichung von HRID 60168
[Si:1]([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](Cl)[N:21]=[CH:22][C:15]=2[N:14]([CH3:33])[C:13]1=[O:34])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].CN(C)CC(O)=O.[Cl:48][C:49]1[CH:50]=[C:51]([OH:55])[CH:52]=[CH:53][CH:54]=1>O1CCOCC1.[Cu]I>[Si:1]([O:8][CH2:9][CH2:10][CH2:11][N:12]1[C:17](=[O:18])[C:16]2[CH:19]=[C:20]([O:55][C:51]3[CH:52]=[CH:53][CH:54]=[C:49]([Cl:48])[CH:50]=3)[N:21]=[CH:22][C:15]=2[N:14]([CH3:33])[C:13]1=[O:34])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3]

Komponenten

7

Edukt 4

HCID 673N,N-DimethylglycineHCID 79333-ChlorophenolHCID 10796Cesium carbonateHCID 1317370763-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-((4-chlorophenyl) (hydroxy)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione2×

Produkt 1

HCID 1317370843-(3-(tert-butyldimethylsilyloxy)propyl)-6-(3-chlorophenoxy)-1-methyl pyrido[3,4-d]pyrimidine-2,4(1H,3H)-dioneAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

To a mixture of 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (See Compound 49, step 3, 383 mg, 1 mmol) CuI (24.7 mg, 0.13 mmol), Cs2CO3 (650 mg, 2 mmol), 2-(dimethylamino)acetic acid (51.5 mg, 0.5 mmol) in dioxane (6 mL) was added 3-chlorophenol (192 mg, 1.5 mmol). The reaction was heated at 140° C. (MW) for 2.5 h, cooled to RT and filtered through a pad of Celite. The filtrate was diluted with EA (20 mL) and water (20 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (2:1) to give 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-(3-chlorophenoxy)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (300 mg, 63% yield) as a solid. LCMS: MH+ 476 and TR=2.377 min.

Aufarbeitung

  1. temperatureThe reaction was heated at 140° C. (MW) for 2.5 h
  2. filtrationfiltered through a pad of Celite
  3. additionThe filtrate was diluted with EA (20 mL) and water (20 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated to a residue which
  6. customwas purified by chromatography
  7. washeluted with PE/EA (2:1)

Quellen und Nachweise

ORD-Eintrag
ord-0821a4ce4fe24f87bc6825c2e7befbac
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440973B2

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