Water → HCID 118006196, Verbindung

HRID 926582

Reaktionsgleichung

Reaktionsgleichung von HRID 926582
[N:1]1([C:6]2[CH:26]=[CH:25][C:9]([CH2:10][C:11]3[C:12]([O:23][CH3:24])=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17](I)=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.[C:27]([CH:35]1[CH2:40][CH2:39][N:38]([C:41](=[O:43])[CH3:42])[CH2:37][CH2:36]1)(=[O:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(=O)=O.CC(C)=O.O>O1CCCC1.C(OCC)(=O)C>[N:1]1([C:6]2[CH:26]=[CH:25][C:9]([CH2:10][C:11]3[C:12]([O:23][CH3:24])=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17]([C:27]([OH:34])([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:35]3[CH2:40][CH2:39][N:38]([C:41](=[O:43])[CH3:42])[CH2:37][CH2:36]3)=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1

Komponenten

7

Edukt 4

HCID 962WaterHCID 27407141-Acetyl-4-benzoylpiperidine2×HCID 18522661Acetone cardiceHCID 118006163HCID 118006163, Verbindung2×

Produkt 1

HCID 118006196HCID 118006196, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
23 °C

Versuchsvorschrift

A solution of isopropylmagnesium chloride-lithium chloride complex in tetrahydrofuran (1.3 M, 0.70 mL, 0.92 mmol) was added dropwise to a stirring mixture containing 3-(4-(1H-imidazol-1-yl)benzyl)-4-chloro-6-iodo-2-methoxyquinoline (350 mg, 0.736 mmol, Intermediate 17: step c) and 1-(4-benzoylpiperidin-1-yl)ethanone (170 mg, 0.736 mmol, Intermediate 18) in tetrahydrofuran (7.4 mL) at −35° C. (dry ice-acetone cooling bath). The cooling bath was allowed to slowly warm to 23° C. After 16 hours, water (30 mL) and ethyl acetate (30 mL) were added. The layers were separated. The aqueous layer was extracted with ethyl acetate (30 mL) and the organic layers were combined. The combined solution was dried with sodium sulfate and the dried solution was filtered. Silica gel (2 g) was added to the filtrate and the mixture was concentrated by rotary evaporation to afford a free-flowing powder. The powder was loaded onto a silica gel column for flash column chromatography purification. Elution with ethyl acetate initially, grading to 10% methanol-ethyl acetate provided the title compound as an impure off-white solid. The impure solid was further purified by RP-HPLC eluting initially with 5% acetonitrile-water (containing 0.05% trifluoroacetic acid), grading to 95% acetonitrile-water (containing 0.05% trifluoroacetic acid) to provide the title compound as a white solid after partitioning the twice purified material between dichloromethane-saturated aqueous sodium bicarbonate solution, separating the layers, drying the organic layer with sodium sulfate, filtering the dried solution, and concentrating the filtrate to dryness. MS (ESI): 581.1 [M+H]+.

Aufarbeitung

  1. customThe layers were separated
  2. extractionThe aqueous layer was extracted with ethyl acetate (30 mL)
  3. dry with materialThe combined solution was dried with sodium sulfate
  4. filtrationthe dried solution was filtered
  5. additionSilica gel (2 g) was added to the filtrate
  6. concentrationthe mixture was concentrated by rotary evaporation
  7. customto afford a free-flowing powder
  8. customThe powder was loaded onto a silica gel column for flash column chromatography purification
  9. washElution with ethyl acetate initially

Quellen und Nachweise

ORD-Eintrag
ord-6e0bce005ca04080b74854791901d999
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09284308B2

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