Pyridine → N-(2-Chloro-4-((6-cyano-7-(((2S)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N'-cyclopropylurea

HRID 1010298Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1010298
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:20][C@@H:21]([OH:28])[CH2:22][N:23]([CH2:26][CH3:27])[CH2:24][CH3:25])=[C:14]([C:17]#[N:18])[CH:15]=3)[N:10]=[CH:9][CH:8]=2)=[CH:4][C:3]=1[Cl:31].[N:32]1[CH:37]=C[CH:35]=[CH:34][CH:33]=1.ClC(OC1C=CC=CC=1)=[O:40].C1(N)CC1.C(=O)(O)[O-].[Na+]>CN(C)C=O.C(OCC)(=O)C>[Cl:31][C:3]1[CH:4]=[C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:20][C@@H:21]([OH:28])[CH2:22][N:23]([CH2:26][CH3:27])[CH2:24][CH3:25])=[C:14]([C:17]#[N:18])[CH:15]=3)[N:10]=[CH:9][CH:8]=2)[CH:29]=[CH:30][C:2]=1[NH:1][C:37]([NH:32][CH:33]1[CH2:35][CH2:34]1)=[O:40]

Komponenten

8

Edukt 5

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 69828CyclopropylamineHCID 516892Sodium BicarbonateHCID 672019954-(4-amino-3-chlorophenoxy)-6-cyano-7-(((2S)-3-(diethylamino)-2-hydroxypropyl)oxy)quinoline

Produkt 1

HCID 67202245N-(2-Chloro-4-((6-cyano-7-(((2S)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N'-cyclopropylureaAusbeute 40,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

After dissolving 4-(4-amino-3-chlorophenoxy)-6-cyano-7-(((2S)-3-(diethylamino)-2-hydroxypropyl)oxy)quinoline (78.6 mg, 0.18 mmol) in dimethylformamide (1 ml) under a nitrogen atmosphere, pyridine (0.022 ml, 0.27 mmol) and phenyl chloroformate (0.028 ml, 0.22 mmol) were added dropwise at room temperature, and the mixture was stirred for 1 hour. Cyclopropylamine (0.10 ml) was added dropwise, and the mixture was further stirred overnight. The reaction solution was distributed between ethyl acetate and saturated aqueous sodium bicarbonate, and the organic layer was washed with water and saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off, the residue was subjected to silica gel column chromatography (eluent-ethyl acetate), the fraction containing the target substance was concentrated, suspended in ethyl acetate and diluted with hexane, and the crystals were filtered out and blow-dried to obtain the title compound (37.8 mg, 0.072 mmol, 40.5%) as light yellow crystals.

Aufarbeitung

  1. waitthe mixture was further stirred overnight
  2. washthe organic layer was washed with water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationThe solvent was distilled off
  5. additionthe fraction containing the target substance
  6. concentrationwas concentrated
  7. additiondiluted with hexane
  8. filtrationthe crystals were filtered out and
  9. customblow-dried

Quellen und Nachweise

ORD-Eintrag
ord-00a822c12a6b4ee9a242701ece80f00a
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07973160B2

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