Ethanolamine → 2-(3-Imidazo[1,2-a]pyridin-6-ylmethyl-imidazo[1,2-b]pyridazin-6-ylamino)-ethanol

HRID 69173

Reaktionsgleichung

Reaktionsgleichung von HRID 69173
[CH2:1]([CH2:3][NH2:4])[OH:2].Cl[C:6]1[CH:7]=[CH:8][C:9]2[N:10]([C:12]([CH2:15][C:16]3[CH:17]=[CH:18][C:19]4[N:20]([CH:22]=[CH:23][N:24]=4)[CH:21]=3)=[CH:13][N:14]=2)[N:11]=1.[F-].[K+]>CN1C(=O)CCC1.CCOC(C)=O>[N:24]1[CH:23]=[CH:22][N:20]2[CH:21]=[C:16]([CH2:15][C:12]3[N:10]4[N:11]=[C:6]([NH:4][CH2:3][CH2:1][OH:2])[CH:7]=[CH:8][C:9]4=[N:14][CH:13]=3)[CH:17]=[CH:18][C:19]=12

Komponenten

6

Edukt 3

HCID 700EthanolamineHCID 522689Potassium FluorideHCID 442085716-Chloro-3-imidazo[1,2-a]pyridin-6-ylmethyl-imidazo[1,2-b]pyridazine

Produkt 1

HCID 579173572-(3-Imidazo[1,2-a]pyridin-6-ylmethyl-imidazo[1,2-b]pyridazin-6-ylamino)-ethanol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
180 °C

Versuchsvorschrift

Ethanolamine (277 μL, 4.55 mmol) was added to a solution of (6-Chloro-3-imidazo[1,2-a]pyridin-6-ylmethyl-imidazo[1,2-b]pyridazine (Example 74, 65 mg, 0.228 mmol) and KF (67 mg, 1.138 mmol) in NMP (1.5 mL). The RM was stirred at 180° C. for 2 h. The mixture was diluted with EtOAc and washed with 1 M Na2CO3 (1×) and water (3×). The aqueous layer was extracted with EtOAc (×2). The combined organic layer was dried over Na2SO4, filtered and concentrated. The aqueous phase was further extracted with DCM (4×). The organic layer was then dried over Na2SO4, filtered and concentrated. The combined residues were purified by preparative LCMS to afford the title compound as a yellow oil (tR 2.62 min (conditions 4), MH+=309.1, 1H-NMR in DMSO-d6: 8.84 (s, 1H); 8.28 (d, 1H); 8.16 (d, 1H); 7.95 (m, 3H); 7.86 (s, 1H); 7.72 (m, 1H); 7.16 (d, 1H); 4.40 (s, 2H); 3.52 (t, 2H); 3.32 (m, 2H)).

Aufarbeitung

  1. washwashed with 1 M Na2CO3 (1×) and water (3×)
  2. extractionThe aqueous layer was extracted with EtOAc (×2)
  3. dry with materialThe combined organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. extractionThe aqueous phase was further extracted with DCM (4×)
  7. dry with materialThe organic layer was then dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe combined residues were purified by preparative LCMS

Quellen und Nachweise

ORD-Eintrag
ord-44bf633d8ed549dd8e7ffb5933bfb9cc
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822468B2

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