Morpholine → N-[4-chloro-2-fluoro-5-({2-[(morpholin-4-ylacetyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)phenyl]-3-(1-cyano-1-methylethyl)benzamide

HRID 1800528

Reaktionsgleichung

Reaktionsgleichung von HRID 1800528
[Cl:1][C:2]1[C:7]([O:8][C:9]2[N:14]=[C:13]3[S:15][C:16]([NH:18][C:19](=[O:22])[CH2:20]Cl)=[N:17][C:12]3=[CH:11][CH:10]=2)=[CH:6][C:5]([NH:23][C:24](=[O:36])[C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([C:34]#[N:35])([CH3:33])[CH3:32])[CH:26]=2)=[C:4]([F:37])[CH:3]=1.C(N(CC)CC)C.[NH:45]1[CH2:50][CH2:49][O:48][CH2:47][CH2:46]1>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[C:7]([O:8][C:9]2[N:14]=[C:13]3[S:15][C:16]([NH:18][C:19](=[O:22])[CH2:20][N:45]4[CH2:50][CH2:49][O:48][CH2:47][CH2:46]4)=[N:17][C:12]3=[CH:11][CH:10]=2)=[CH:6][C:5]([NH:23][C:24](=[O:36])[C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([C:34]#[N:35])([CH3:32])[CH3:33])[CH:26]=2)=[C:4]([F:37])[CH:3]=1

Komponenten

6

Edukt 3

HCID 8083MorpholineHCID 8471TriethylamineHCID 86646016N-[4-chloro-5-({2-[(chloroacetyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-fluorophenyl]-3-(1-cyano-1-methylethyl)benzamide

Produkt 1

HCID 59507019N-[4-chloro-2-fluoro-5-({2-[(morpholin-4-ylacetyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)phenyl]-3-(1-cyano-1-methylethyl)benzamideAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

N-[4-Chloro-5-({2-[(chloroacetyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-fluorophenyl]-3-(1-cyano-1-methylethyl)benzamide synthesized above was dissolved in tetrahydrofuran (3.0 mL), triethylamine (85.6 μL, 0.621 mmol) and morpholine(54.3 μL, 0.621 mmol) were added, and the mixture was stirred at 80° C. for 8 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (10 mL), washed with water (10 mL) and saturated brine (10 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→85/15), and the obtained solution was concentrated under reduced pressure. The residue was triturated with ethyl acetate/hexane to give the title compound (101 mg, 80%) as a colorless amorphous powder.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water (10 mL) and saturated brine (10 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationThe insoluble material was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→85/15)
  7. concentrationthe obtained solution was concentrated under reduced pressure
  8. customThe residue was triturated with ethyl acetate/hexane

Quellen und Nachweise

ORD-Eintrag
ord-20d118f9d4264787b4a4809e7e5acb22
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08344135B2

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