Diisopropylamine → 5-[5-(3-{[4-(2-{[Tert-butyl(dimethyl)silyl]oxy}ethoxy)pyrimidin-2-yl]amino}-5-methylphenyl)-1,3-thiazol-2-yl]-2,2-dimethyl-1,3-dioxan-5-ol

HRID 410709Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 410709
C(NC(C)C)(C)C.C([Li])CCC.[Si:13]([O:20][CH2:21][CH2:22][O:23][C:24]1[CH:29]=[CH:28][N:27]=[C:26]([NH:30][C:31]2[CH:36]=[C:35]([C:37]3[S:41][CH:40]=[N:39][CH:38]=3)[CH:34]=[C:33]([CH3:42])[CH:32]=2)[N:25]=1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].[CH3:43][C:44]1([CH3:51])[O:49][CH2:48][C:47](=[O:50])[CH2:46][O:45]1>O1CCCC1>[Si:13]([O:20][CH2:21][CH2:22][O:23][C:24]1[CH:29]=[CH:28][N:27]=[C:26]([NH:30][C:31]2[CH:36]=[C:35]([C:37]3[S:41][C:40]([C:47]4([OH:50])[CH2:48][O:49][C:44]([CH3:51])([CH3:43])[O:45][CH2:46]4)=[N:39][CH:38]=3)[CH:34]=[C:33]([CH3:42])[CH:32]=2)[N:25]=1)([C:16]([CH3:17])([CH3:18])[CH3:19])([CH3:14])[CH3:15]

Komponenten

6

Edukt 4

HCID 7912DiisopropylamineHCID 27331412,2-Dimethyl-1,3-dioxan-5-oneHCID 672577054-(2-{[tert-butyl(dimethyl)silyl]oxy}ethoxy)-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amineHCID 178418339Butyllithium

Produkt 1

HCID 674315445-[5-(3-{[4-(2-{[Tert-butyl(dimethyl)silyl]oxy}ethoxy)pyrimidin-2-yl]amino}-5-methylphenyl)-1,3-thiazol-2-yl]-2,2-dimethyl-1,3-dioxan-5-olAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To diisopropyl amine (185 μL, 1.29 mmol) in tetrahydrofuran (2.2 mL) at 0° C. was added n-butyllithium (2.2 M in hexanes, 589 μL, 1.29 mmol). The mixture was stirred for 15 minutes, then cooled to −78° C. 4-(2-{[tert-butyl(dimethyl)silyl]oxy}ethoxy)-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine (191 mg, 0.43 mmol), dissolved in tetrahydrofuran (1 mL), was added dropwise over 5 minutes. The mixture was stirred for 30 minutes at −78° C., then 2,2-dimethyl-1,3-dioxan-5-one (57 μL, 0.47 mmol) was added dropwise. The reaction was stirred for 2 h, and then quenched with saturated aqueous ammonium chloride. The mixture was extracted with ethyl acetate (3×), and the combined organic fractions were dried over sodium sulfate, filtered, and concentrated. Purification by column chromatography on silica gel (Biotage 25 G, eluting with 0:100 to 100:0 ethyl acetate:hexanes) gave 5-[5-(3-{[4-(2-{[tert-butyl(dimethyl)silyl]oxy}ethoxy)pyrimidin-2-yl]amino}-5-methylphenyl)-1,3-thiazol-2-yl]-2,2-dimethyl-1,3-dioxan-5-ol (185 mg, 0.32 mmol, 75% yield) as a pale yellow solid. MS ESI: [M+H]+ m/z 573.3.

Aufarbeitung

  1. additionwas added dropwise over 5 minutes
  2. stirringThe mixture was stirred for 30 minutes at −78° C.
  3. stirringThe reaction was stirred for 2 h
  4. customquenched with saturated aqueous ammonium chloride
  5. extractionThe mixture was extracted with ethyl acetate (3×)
  6. dry with materialthe combined organic fractions were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by column chromatography on silica gel (Biotage 25 G, eluting with 0:100 to 100:0 ethyl acetate:hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-0c1aa3450a534bbb867a9a5f9980ab5c
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08759366B2

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