Tetrahydrofuran → 3-[3-chloro-5-(5-fluoro-2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

HRID 1432714Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1432714
[Cl:1][C:2]1[CH:6]=[C:5]([C:7]2[N:8]([CH3:12])[N:9]=[CH:10][N:11]=2)[S:4][C:3]=1[C:13]1[N:17]2[N:18]=[C:19]([CH3:27])[CH:20]=[C:21]([CH:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[C:16]2=[N:15][C:14]=1[CH3:28].C1COCC1.[Li]C(C)(C)C.[F:39]NS(C1C=CC=CC=1)(=O)=O>CCOC(C)=O>[Cl:1][C:2]1[CH:6]=[C:5]([C:7]2[N:8]([CH3:12])[N:9]=[C:10]([F:39])[N:11]=2)[S:4][C:3]=1[C:13]1[N:17]2[N:18]=[C:19]([CH3:27])[CH:20]=[C:21]([CH:22]([CH2:23][CH3:24])[CH2:25][CH3:26])[C:16]2=[N:15][C:14]=1[CH3:28]

Komponenten

6

Edukt 4

HCID 8028Tetrahydrofuran2×HCID 15373214N-FluorobenzenesulfonamideHCID 579330443-[3-chloro-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178418306HCID 178418306, Verbindung

Produkt 1

HCID 579329143-[3-chloro-5-(5-fluoro-2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineAusbeute 22,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a −78° C. solution of 3-[3-chloro-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.40 g, 0.72 mmol) and THF (8 mL) is added 1.7 M tert-BuLi (0.47 mL, 0.80 mmol). After 30 minutes the solution is transferred via a cannula into a solution of N-fluorobenzenesulfonamide (0.40 g, 1.25 mmol) and THF. After 30 minutes the solution warmed to ambient temperature. The solution is diluted with EtOAc (40 mL), washed with water (30 mL), brine (30 mL), dried over MgSO4, filtered and concentrated. The solution is purified by ISCO (20%-30% EtOAc gradient) furnish the title compound (0.068 g, 0.16 mmol, 16%). 1H NMR (CDCl3) δ 0.87 (t, J=7.5 Hz, 6H), 1.71-1.93 (m, 4H), 2.53 (s, 3H), 2.54 (s, 3H), 3.26-3.36 (m, 1H), 4.08 (d J=2.7 Hz, 3H), 6.75 (s, 1H), 7.97 (s, 1H). LC/MS (m/z): calcd. for C20H22ClFN6S (M+H)+: 433.2; found: 433.2.

Aufarbeitung

  1. washwashed with water (30 mL), brine (30 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe solution is purified by ISCO (20%-30% EtOAc gradient)

Quellen und Nachweise

ORD-Eintrag
ord-27f279734e224bef8cef3ad1c6311f21
Quelldatensatz
uspto-grants-2009_11
Patentnummer
US07612067B2

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