Dimethylformamide → Tert-butyl 4-(8-morpholino-2-(quinolin-2-ylethynyl)imidazo[1,2-b]pyridazin-3-yl)benzoate

HRID 718584

Reaktionsgleichung

Reaktionsgleichung von HRID 718584
[C:1]([C:3]1[N:4]=[C:5]2[C:10]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:9][CH:8]=[N:7][N:6]2[C:17]=1[C:18]1[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:20][CH:19]=1)#[CH:2].Br[C:32]1[CH:41]=[CH:40][C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[N:33]=1.CN(C=O)C.CCN(C(C)C)C(C)C>[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[O:14]1[CH2:15][CH2:16][N:11]([C:10]2[C:5]3[N:6]([C:17]([C:18]4[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])=[CH:20][CH:19]=4)=[C:3]([C:1]#[C:2][C:32]4[CH:41]=[CH:40][C:39]5[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=5)[N:33]=4)[N:4]=3)[N:7]=[CH:8][CH:9]=2)[CH2:12][CH2:13]1

Komponenten

8

Edukt 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 27627562-BromoquinolineHCID 117732463tert-Butyl 4-(2-ethynyl-8-morpholinoimidazo[1,2-b]pyridazin-3-yl)benzoate

Produkt 1

HCID 117728418Tert-butyl 4-(8-morpholino-2-(quinolin-2-ylethynyl)imidazo[1,2-b]pyridazin-3-yl)benzoate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittel

Versuchsvorschrift

A mixture of compound 17a (0.23 g, 0.57 mmol) and 2-bromoquinoline (1.0 g, 4.8 mmol) in a vial was evacuated and back flushed with Argon. Dry DMF (5 mL) and DIEA (0.99 mL, 5.7 mmol) were added via syringe and the mixture was deoxygenated by bubbling Argon gas through the stirred solution for 5 min. To the mixture were added CuI (5.4 mg, 0.028 mmol) and dichlorobis(triphenylphosphine)palladium(II) (40 mg, 0.057 mmol). The resulting mixture was stirred at rt for 1 h, and was poured into water (50 mL). The mixture was extracted with EtOAc (3×30 mL). The combined organic extracts were washed with water (20 mL) and brine (2×20 mL). The organic layer was concentrated, and the resulting residue was purified by flash column chromatography on silica gel (20-60% EtOAc/heptane) to give tert-butyl 4-(8-morpholino-2-(quinolin-2-ylethynyl)imidazo[1,2-b]pyridazin-3-yl)benzoate as a yellow solid.

Aufarbeitung

  1. customwas evacuated
  2. customback flushed with Argon
  3. customthe mixture was deoxygenated
  4. customby bubbling Argon gas through the stirred solution for 5 min
  5. extractionThe mixture was extracted with EtOAc (3×30 mL)
  6. washThe combined organic extracts were washed with water (20 mL) and brine (2×20 mL)
  7. concentrationThe organic layer was concentrated
  8. customthe resulting residue was purified by flash column chromatography on silica gel (20-60% EtOAc/heptane)

Quellen und Nachweise

ORD-Eintrag
ord-730fdae97bef4084a60a9d91da0963ba
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09193736B2

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