Cesium carbonate → 8-(1-Ethyl-propyl)-3-(5-fluoro-3-methyl-benzo[b]thiophen-2-yl)-6-methyl-2-trifluoromethyl-imidazo[1,2-b]pyridazine

HRID 226044Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 226044
[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2].Br[C:21]1[S:25][C:24]2[CH:26]=[CH:27][C:28]([F:30])=[CH:29][C:23]=2[C:22]=1[CH3:31].C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CN1C(=O)CCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([C:13]([C:21]3[S:25][C:24]4[CH:26]=[CH:27][C:28]([F:30])=[CH:29][C:23]=4[C:22]=3[CH3:31])=[C:14]([C:16]([F:18])([F:19])[F:17])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2]

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 667212022-Bromo-5-fluoro-3-methylbenzo[b]thiopheneHCID 688409078-(1-Ethyl-propyl)-6-methyl-2-trifluoromethyl-imidazo[1,2-b]pyridazine

Produkt 1

HCID 577526508-(1-Ethyl-propyl)-3-(5-fluoro-3-methyl-benzo[b]thiophen-2-yl)-6-methyl-2-trifluoromethyl-imidazo[1,2-b]pyridazineAusbeute 10 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

To a dry 10 ml round bottom flask with reflux condenser containing 8-(1-ethyl-propyl)-6-methyl-2-trifluoromethyl-imidazo[1,2-b]pyridazine (150 mg, 0.690 mmol), 2-bromo-5-fluoro-3-methyl-benzo[b]thiophene (186.1 mg, 0.759 mmol), and Cs2CO3 (472 mg, 1.45 mmol) in NMP (1.1 ml). The mixture is degassed with bubbling N2 for 15 min. Then add Pd2(dba)3 (32 mg, 0.0345 mmol) and PPh3 (36.2 mg, 0.138 mmol). Heat the reaction mixture at 130° C. and stir overnight. Dilute with H2O; extract with EtOAc (3×20 ml); dried (Na2SO4), filter and purify by HPLC to give title compound (29.5 mg, 0.068 mmol, 10%). 1H NMR (CDCl3): 0.931 (t, J=7.6 Hz, 6H), 1.912 (m, 4H), 2.286 (s, 3H), 2.552 (s, 3H), 3.386 (m, 1H), 6.877 (s, 1H), 7.224 (td, J=2.4, 9.0 Hz, 1H), 7.50 (dd, J=2.9, 9.8 Hz, 1H), 7.842 (dd, J=4.9, 9.0 Hz, 1H) ppm. ES-MS (m/z): calcd for C22H21F4N3S (M+H)+: 435.39. found: 436.2.

Aufarbeitung

  1. temperatureTo a dry 10 ml round bottom flask with reflux condenser
  2. customThe mixture is degassed with bubbling N2 for 15 min
  3. extractionextract with EtOAc (3×20 ml)
  4. dry with materialdried (Na2SO4)
  5. filtrationfilter
  6. custompurify by HPLC

Quellen und Nachweise

ORD-Eintrag
ord-417002ea858b4115a604cba58048daec
Quelldatensatz
uspto-grants-2009_07
Patentnummer
US07557103B2

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