Lithium diisopropylamide → 1-(6-Bromopyridin-3-yl)-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethanol

HRID 410689Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 410689
C([N-]C(C)C)(C)C.[Li+].[CH3:9][C:10]1[CH:11]=[C:12]([NH:21][C:22]2[N:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][N:23]=2)[CH:13]=[C:14]([C:16]2[S:20][CH:19]=[N:18][CH:17]=2)[CH:15]=1.[Br:32][C:33]1[N:38]=[CH:37][C:36]([C:39](=[O:41])[CH3:40])=[CH:35][CH:34]=1>C1COCC1>[Br:32][C:33]1[N:38]=[CH:37][C:36]([C:39]([C:19]2[S:20][C:16]([C:14]3[CH:13]=[C:12]([NH:21][C:22]4[N:27]=[C:26]([C:28]([F:29])([F:31])[F:30])[CH:25]=[CH:24][N:23]=4)[CH:11]=[C:10]([CH3:9])[CH:15]=3)=[CH:17][N:18]=2)([OH:41])[CH3:40])=[CH:35][CH:34]=1

Komponenten

5

Edukt 3

HCID 2724682Lithium diisopropylamideHCID 156681955-Acetyl-2-bromopyridineHCID 58456403N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine2×

Produkt 1

HCID 866582581-(6-Bromopyridin-3-yl)-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethanolAusbeute 21,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

THF (10 ml) was cooled to −78° C., and lithium diisopropylamide (4.13 ml, 7.43 mmol) was added. N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (INTERMEDIATE 4, 1.00 g, 2.97 mmol) in THF (10 ml) was added dropwise, and the reaction was stirred at −78° C. for 30 min. 1-(6-Bromopyridin-3-yl)ethanone (0.595 g, 2.97 mmol) in THF (5 ml) was subsequently added in one portion. The reaction was stirred for 10 min at −78° C. The dry ice bath was removed, and the reaction was allowed to warm to room temperature. The dark brown reaction mixture was quenched with aqueous saturated NH4Cl and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated. Chromatography on silica gel (Biotage 100 g SNAP, 0-30% EtOAc/toluene) afforded 1-(6-bromopyridin-3-yl)-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethanol (348 mg, 0.649 mmol, 21.8% yield) as a yellow solid. MS ESI: [M+H]+ m/z 538.0.

Aufarbeitung

  1. stirringThe reaction was stirred for 10 min at −78° C
  2. customThe dry ice bath was removed
  3. temperatureto warm to room temperature
  4. customThe dark brown reaction mixture was quenched with aqueous saturated NH4Cl
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-e130183dbc334c9ca11479236f9f6c63
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08759366B2

Notizen zur Reaktion

Wird geladen…