Lithium diisopropylamide → HCID 67432981, Verbindung

HRID 1040202Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1040202
[CH3:1][C:2]1[CH:3]=[C:4]([NH:13][C:14]2[N:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][N:15]=2)[CH:5]=[C:6]([C:8]2[S:12][CH:11]=[N:10][CH:9]=2)[CH:7]=1.[Li+].CC([N-]C(C)C)C.[CH3:32][C:33]1([CH3:44])[C:42](=[O:43])[CH2:41][CH2:40][CH2:39][C:34]21[O:38][CH2:37][CH2:36][O:35]2>C1COCC1.[Cl-].[NH4+]>[CH3:32][C:33]1([CH3:44])[C:42]([C:11]2[S:12][C:8]([C:6]3[CH:5]=[C:4]([NH:13][C:14]4[N:19]=[C:18]([C:20]([F:21])([F:23])[F:22])[CH:17]=[CH:16][N:15]=4)[CH:3]=[C:2]([CH3:1])[CH:7]=3)=[CH:9][N:10]=2)([OH:43])[CH2:41][CH2:40][CH2:39][C:34]21[O:35][CH2:36][CH2:37][O:38]2

Komponenten

6

Edukt 3

HCID 2724682Lithium diisopropylamideHCID 109977176,6-dimethyl-1,4-dioxaspiro[4.5]decan-7-oneHCID 58456403N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine

Produkt 1

HCID 67432981HCID 67432981, VerbindungAusbeute 57,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 25517Ammonium ChlorideLösungsmittel

Versuchsvorschrift

To a stirred solution of INTERMEDIATE 4 (1.09 g, 3.24 mmol) in THF (17 mL) was added LDA (2M, 4.86 mL, 9.72 mmol) dropwise at −78° C. The orange solution was left to stir for 30 min at that temperature, treated with 6,6-dimethyl-1,4-dioxaspiro[4.5]decan-7-one (0.72 g, 3.9 mmol) in THF (4.5 mL) dropwise, and allowed to warm to room temperature as the bath did. The reaction mixture was diluted with saturated ammonium chloride solution, and extracted with EtOAc (3×). The combined organics were washed with brine, dried (sodium sulfate), filtered concentrated, and purified by column chromatography on silica to afford 6,6-dimethyl-7-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decan-7-ol (964 mg, 1.85 mmol) as a light yellow foam. MS ESI: [M+H]+ m/z 521.1.

Aufarbeitung

  1. waitThe orange solution was left
  2. extractionextracted with EtOAc (3×)
  3. washThe combined organics were washed with brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by column chromatography on silica

Quellen und Nachweise

ORD-Eintrag
ord-9d45d762adf94cb690d67d9e4cc19925
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08551984B2

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