Water → N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-vinylpyridin-2-amine

HRID 1621448

Reaktionsgleichung

Reaktionsgleichung von HRID 1621448
F[C:2]1[C:7]([C:8]2[N:16]=[C:15]([CH3:17])[N:14]=[C:13]3[C:9]=2[N:10]=[CH:11][N:12]3[CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)=[CH:6][C:5]([CH:24]=[CH2:25])=[CH:4][N:3]=1.[NH2:26][C:27]1[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[N:31][CH:32]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.O>C1COCC1>[CH3:34][O:33][C:30]1[N:31]=[CH:32][C:27]([NH:26][C:2]2[C:7]([C:8]3[N:16]=[C:15]([CH3:17])[N:14]=[C:13]4[C:9]=3[N:10]=[CH:11][N:12]4[CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)=[CH:6][C:5]([CH:24]=[CH2:25])=[CH:4][N:3]=2)=[CH:28][CH:29]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 811216-Methoxy-3-pyridinylamineHCID 2733832Lithium HexamethyldisilazideHCID 595484346-(2-fluoro-5-vinylpyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Produkt 1

HCID 59548466N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-vinylpyridin-2-amineAusbeute 31,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

6-(2-Fluoro-5-vinylpyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (1.007 g, 2.967 mmol) and 5-amino-2-methoxypyridine (0.369 g, 2.97 mmol) were dissolved in THF (25 mL) and the reaction flask was cooled in an ice water bath. Then, LiHMDS (Aldrich, St. Louis, Mo., 1.0 M in THF, 9.0 mL, 9.0 mmol) was added via syringe, and the reaction was stirred under nitrogen for 35 minutes. Then, it was poured into water (50 mL), and the layers were separated. The aqueous phase was extracted with DCM, and the organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and purified on a silica gel column (40:1 DCM/2N ammonia in MeOH to 30:1 DCM/2N ammonia in MeOH) to give N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-vinylpyridin-2-amine (410.3 mg, 85% purity, 20% yield over 2 steps). MS (ESI pos. ion) m/z 444 (M+H)+.

Aufarbeitung

  1. temperaturethe reaction flask was cooled in an ice water bath
  2. customthe layers were separated
  3. extractionThe aqueous phase was extracted with DCM
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified on a silica gel column (40:1 DCM/2N ammonia in MeOH to 30:1 DCM/2N ammonia in MeOH)

Quellen und Nachweise

ORD-Eintrag
ord-f5c063cded7f4ac68e1b401e21c68ba2
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08772480B2

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