Lithium diisopropylamide → HCID 67261191, Verbindung

HRID 410571Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 410571
[Li+].CC([N-]C(C)C)C.[CH:9]1([C:12]2[C:17]([F:18])=[CH:16][N:15]=[C:14]([NH:19][C:20]3[CH:25]=[C:24]([C:26]4[S:30][CH:29]=[N:28][CH:27]=4)[CH:23]=[C:22]([F:31])[CH:21]=3)[N:13]=2)[CH2:11][CH2:10]1.[C:32]([Si:36]([CH3:43])([CH3:42])[O:37][CH2:38][C:39]([CH3:41])=[O:40])([CH3:35])([CH3:34])[CH3:33]>O1CCCC1>[Si:36]([O:37][CH2:38][C:39]([C:29]1[S:30][C:26]([C:24]2[CH:23]=[C:22]([F:31])[CH:21]=[C:20]([NH:19][C:14]3[N:13]=[C:12]([CH:9]4[CH2:11][CH2:10]4)[C:17]([F:18])=[CH:16][N:15]=3)[CH:25]=2)=[CH:27][N:28]=1)([OH:40])[CH3:41])([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:43])[CH3:42]

Komponenten

5

Edukt 3

HCID 2724682Lithium diisopropylamideHCID 41249691-(tert-Butyldimethylsilyloxy)-2-propanoneHCID 67257916HCID 67257916, Verbindung

Produkt 1

HCID 67261191HCID 67261191, VerbindungAusbeute 64 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Versuchsvorschrift

LDA (0.757 mL, 1.362 mmol) was added to tetrahydrofuran (4 mL) at −78° C. After 15 minutes at −78° C., a solution of the product of Step 4 (150 mg, 0.454 mmol) in tetrahydrofuran (4 mL) was added dropwise. After 30 minutes at −78° C., a solution of 1-{[tert-butyl(dimethyl)-silyl]oxy}acetone (0.110 mL, 0.568 mmol) in tetrahydrofuran (4 mL) was added dropwise at −78° C. The reaction mixture was allowed to warm to ambient temperature. After 1 hour, the reaction mixture was quenched with saturated ammonium chloride, diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel, eluting with ethyl acetate and hexanes to afford 1-{[tert-butyl(dimethyl)silyl]oxy}-2-(5-{3-[(4-cyclopropyl-5-fluoropyrimidin-2-yl)amino]-5-fluorophenyl}-1,3-thiazol-2-yl)propan-2-ol (150 mg, 0.29 mmol, 64%). MS ESI: [M+H]+ m/z 519.2.

Aufarbeitung

  1. waitAfter 30 minutes at −78° C.
  2. waitAfter 1 hour
  3. customthe reaction mixture was quenched with saturated ammonium chloride
  4. additiondiluted with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography on silica gel
  10. washeluting with ethyl acetate and hexanes

Quellen und Nachweise

ORD-Eintrag
ord-3a02a0dfe6f94975b34612ae44ae066f
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08759366B2

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