Water → 2-(3-ethynyl-quinolin-6-yloxy)-2-methylsulfanyl-N-(1-prop-2-ynyloxymethyl-cyclobutyl)-acet-amide

HRID 1962889Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1962889
[H-].[Na+].[C:3]([C:5]1[CH:6]=[N:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH:16]([S:26][CH3:27])[C:17]([NH:19][C:20]1([CH2:24][OH:25])[CH2:23][CH2:22][CH2:21]1)=[O:18])=[CH:10][CH:9]=2)#[CH:4].[CH2:28](Br)[C:29]#[CH:30].O>C1COCC1>[C:3]([C:5]1[CH:6]=[N:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH:16]([S:26][CH3:27])[C:17]([NH:19][C:20]1([CH2:24][O:25][CH2:30][C:29]#[CH:28])[CH2:23][CH2:22][CH2:21]1)=[O:18])=[CH:10][CH:9]=2)#[CH:4]

Komponenten

6

Edukt 4

HCID 962WaterHCID 7842Propargyl bromideHCID 24758Sodium hydrideHCID 595653282-(3-ethynyl-quinolin-6-yloxy)-N-(1-hydroxymethyl-cyclobutyl)-2-methylsulfanyl-acetamide

Produkt 1

HCID 595653102-(3-ethynyl-quinolin-6-yloxy)-2-methylsulfanyl-N-(1-prop-2-ynyloxymethyl-cyclobutyl)-acet-amideAusbeute 15,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

NaH (172 mg, 60% in oil) was added to a solution of 2-(3-ethynyl-quinolin-6-yloxy)-N-(1-hydroxymethyl-cyclobutyl)-2-methylsulfanyl-acetamide (850 mg) in THF (50 ml), at room temperature, under nitrogen atmosphere. The mixture was stirred until gas evolution ceased (30 min). Propargyl bromide (638 mg, 80% toluene solution) was added and the mixture was stirred at 40° C. during 3 hours, and then after cooling to room temperature poured into water and extracted with ethyl acetate. The combined organic layers were washed with water, brine, dried over sodium sulphate anhydrous, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate/CH2Cl2, 1/1/1) to give 2-(3-ethynyl-quinolin-6-yloxy)-2-methylsulfanyl-N-(1-prop-2-ynyloxymethyl-cyclobutyl)-acet-amide (146 mg) as slightly brown oil. 1H NMR (CDCl3) δ ppm: 8.82 (1H, d); 8.18 (1H, d); 8.03 (1H, d); 7.44 (1H, dd); 7.21 (1H, d); 6.88 (1H, br s); 5.62 (1H, s); 4.14 (2H, s); 3.84-3.74 (2H, dd, AB system); 3.28 (1H, s); 2.49-2.13 (4H, m); 2.42 (1H, s); 2.19 (3H, s); 2.01-1.79 (2H, m).

Aufarbeitung

  1. custom(30 min)
  2. stirringthe mixture was stirred at 40° C. during 3 hours
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layers were washed with water, brine
  5. dry with materialdried over sodium sulphate anhydrous
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate/CH2Cl2, 1/1/1)

Quellen und Nachweise

ORD-Eintrag
ord-f309f6c3436f451e96e22e82b98a2080
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08415272B2

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