Water → 6-(4-(2-(diethylamino)ethoxy)phenyl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine

HRID 1755423Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1755423
[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[N:12]=[C:11]([NH:13][C:14]2[C:15]3[N:16]([CH:27]=[CH:28][N:29]=3)[N:17]=[C:18]([C:20]3[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=3)[CH:19]=2)[CH:10]=[CH:9][CH:8]=1.C([O-])([O-])=O.[K+].[K+].CS(O[CH2:41][CH2:42][N:43]([CH2:46][CH3:47])[CH2:44][CH3:45])(=O)=O.O>CN(C=O)C>[CH2:42]([N:43]([CH2:46][CH3:47])[CH2:44][CH2:45][O:26][C:23]1[CH:24]=[CH:25][C:20]([C:18]2[CH:19]=[C:14]([NH:13][C:11]3[CH:10]=[CH:9][CH:8]=[C:7]([N:3]4[CH2:4][CH2:5][CH2:6][CH:2]4[CH3:1])[N:12]=3)[C:15]3[N:16]([CH:27]=[CH:28][N:29]=3)[N:17]=2)=[CH:21][CH:22]=1)[CH3:41]

Komponenten

6

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 866827512-(Diethylamino)ethyl methanesulfonateHCID 136235684HCID 136235684, Verbindung

Produkt 1

HCID 715267026-(4-(2-(diethylamino)ethoxy)phenyl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amineAusbeute 41,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a mixture of 4-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)phenol (40 mg, 0.1 mmol) and K2CO3 (28 mg, 0.2 mmol) in DMF (5 mL) was added 2-(diethylamino)ethyl methanesulfonate (30 mg, 0.15 mmol). The mixture was heated at 50° C. for 15 h. After cooling, the mixture was poured into water and extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine and dried over MgSO4. After filtration and concentration, the residue was purified by chromatography (silica, EtOAc) to give 6-(4-(2-(diethylamino)ethoxy)phenyl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (20 mg, 40%). 1H NMR (300 MHz, CDCl3): δ 8.59 (s, 1H), 8.06-7.90 (m, 4 h), 7.58 (s, 1H), 7.42 (t, 1H, J=7.6 Hz), 7.03-7.00 (m, 2H), 6.23 (d, 1H, J=7.2 Hz), 6.05 (d, 1H, J=8.1 Hz), 4.57 (brs, 2H), 4.27 (brs, 1H), 3.67 (brs, 1H), 3.52-3.41 (m, 3H), 3.22-3.20 (m, 4 h), 2.16-2.06 (m, 3H), 1.80 (brs, 1H), 1.45 (t, 6H, J=6.9 Hz), 1.28 (d, 3H, J=6.3 Hz). LC/MS: 486 [M+H]+, tR=1.12 min. HPLC: 98.72% at 214 nm, 99.10% at 254 nm, tR=5.46 min.

Aufarbeitung

  1. temperatureAfter cooling
  2. extractionextracted with EtOAc (3×10 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationAfter filtration and concentration
  6. customthe residue was purified by chromatography (silica, EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-064fcf5c0c5747a5b2985d0b56777cdd
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09169259B2

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