Ammonium Chloride → 8-(1-Ethyl-propyl)-2,6-dimethyl-3-[1-methyl-5-(3-methyl-thiophen-2-yl)-1H-pyrrol-2-yl]-imidazo[1,2-b]pyridazine

HRID 1432662Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1432662
Br[C:2]1[N:6]([CH3:7])[C:5]([C:8]2[N:12]3[N:13]=[C:14]([CH3:22])[CH:15]=[C:16]([CH:17]([CH2:20][CH3:21])[CH2:18][CH3:19])[C:11]3=[N:10][C:9]=2[CH3:23])=[CH:4][CH:3]=1.[Br-].[CH3:25][C:26]1[CH:30]=[CH:29][S:28][C:27]=1[Zn+].[NH4+].[Cl-]>C1COCC1>[CH2:18]([CH:17]([C:16]1[C:11]2[N:12]([C:8]([C:5]3[N:6]([CH3:7])[C:2]([C:27]4[S:28][CH:29]=[CH:30][C:26]=4[CH3:25])=[CH:3][CH:4]=3)=[C:9]([CH3:23])[N:10]=2)[N:13]=[C:14]([CH3:22])[CH:15]=1)[CH2:20][CH3:21])[CH3:19]

Komponenten

5

Edukt 3

HCID 25517Ammonium ChlorideHCID 688411313-(5-Bromo-1-methyl-1H-pyrrol-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178429658HCID 178429658, Verbindung

Produkt 1

HCID 579330778-(1-Ethyl-propyl)-2,6-dimethyl-3-[1-methyl-5-(3-methyl-thiophen-2-yl)-1H-pyrrol-2-yl]-imidazo[1,2-b]pyridazineAusbeute 55,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A THF slurry (5 mL) of 3-(5-bromo-1-methyl-1H-pyrrol-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (143 mg, 0.38 mmol) and PdCl2(dppf)-CH2Cl2 complex (Aldrich, 19 mg, 0.023 mmol) is treated with 3-methyl-2-thienyl zinc bromide (Aldrich, 0.5 M in THF, 3.8 mL, 1.9 mmol) then heated to 60° C. for 1 hr. The resulting mixture is poured into sat'd NH4Cl (25 mL) and extracted with diethyl ether (35 mL). The organic extract is washed with aq. NaCl, dried over Na2SO4, filtered, and concentrated. The crude product is purified by chromatography using hexane-ethyl acetate gradient (100% hexane to 15% ethyl acetate in hexane) to elute the product. The material is purified a second time by flash chromatography using hexane-ethyl acetate gradient (100% hexane to 12% ethyl acetate in hexane) to elute the product. Only the fractions containing pure desired product, as judged by MS analysis, are collected and give the title compound (82.6 mg, 55% yield) as an oil. ES-MS (m/z): calc'd for C23H28N4S: 392.20. found 393.1 (M+H)+. 1H NMR (400 mHz, CDCl3): δ 7.28 (d, J=5.3 Hz, 1H), 6.96 (d, J=4.8 Hz, 1H), 6.67 (br s, 1H), 6.39 (d, J=3.5 Hz, 1H), 6.37 (d, J=4.0 Hz, 1H), 3.35 (br s, 1H), 3.33, (s, 3H), 2.52 (s, 3H), 2.51 (s, 3H), 2.26 (s, 3H), 1.89-1.76 (m, 4H), 0.87 (t, J=7.5 Hz, 6H).

Aufarbeitung

  1. extractionextracted with diethyl ether (35 mL)
  2. extractionThe organic extract
  3. washis washed with aq. NaCl
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product is purified by chromatography
  8. washto elute the product
  9. customThe material is purified a second time by flash chromatography
  10. washto elute the product
  11. additionOnly the fractions containing pure desired product
  12. customare collected

Quellen und Nachweise

ORD-Eintrag
ord-19c57ff50bbe4f9aa69cad6061d4e124
Quelldatensatz
uspto-grants-2009_11
Patentnummer
US07612067B2

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