Water → ethyl 4-[2-(4-fluorophenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazin-3-yl]-4H-pyridine-1-carboxylate

HRID 1803874

Reaktionsgleichung

Reaktionsgleichung von HRID 1803874
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]4)=[N:12][N:11]3[CH:23]=2)=[CH:4][CH:3]=1.Cl[C:25]([O:27][CH2:28][CH3:29])=[O:26].O.[N:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]4)=[N:12][N:11]3[C:23]=2[CH:34]2[CH:35]=[CH:36][N:31]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH:32]=[CH:33]2)=[CH:4][CH:3]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 1049Pyridine2×HCID 10928Ethyl chloroformate3×HCID 594069602-(4-Fluorophenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazine

Produkt 1

HCID 59406952ethyl 4-[2-(4-fluorophenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazin-3-yl]-4H-pyridine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a suspension, cooled to about 0° C., of 3.24 g (10.4 mmol) of 2-(4-fluorophenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazine in 7.5 mL of pyridine is added dropwise a solution of 5.0 mL (52 mmol) of ethyl chloroformate. After cooling to room temperature, 10 mL (104 mmol) of ethyl chloroformate and 15 mL of pyridine are added in two portions. After 18 hours, the mixture is diluted with 50 mL of dichloromethane and 20 mL (208 mmol) of ethyl chloroformate are added in three portions over 5 hours. 350 mL of water are then added, and the organic phase is separated out and washed twice with water, dried over sodium sulfate and concentrated under reduced pressure to give 4.5 g of a brownish solid. This solid is triturated in diethyl ether to give 3.5 g of beige-colored crystals. The solid is dissolved in dichloromethane and purified by chromatography on a column of silica gel, eluting with a mixture of 10% methanol in dichloromethane, to give 2.95 g of pale yellow crystals after trituration in diethyl ether, filtering through a sinter funnel and drying under vacuum.

Aufarbeitung

  1. additionare added in three portions over 5 hours
  2. customthe organic phase is separated out and
  3. washwashed twice with water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-691e14969d92485ea8faf68c36d9c0cd
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08354405B2

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