Triethylamine → 5-fluoro-N-[(1S,3S)-3-hydroxycyclohexyl]-2-[3-(methylsulfanyl)phenoxy]nicotinamide

HRID 724300Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 724300
[CH3:1][S:2][C:3]1[CH:4]=[C:5]([CH:17]=[CH:18][CH:19]=1)[O:6][C:7]1[N:15]=[CH:14][C:13]([F:16])=[CH:12][C:8]=1[C:9]([OH:11])=O.C(N(CC)CC)C.[NH2:27][C@H:28]1[CH2:33][CH2:32][CH2:31][C@H:30]([OH:34])[CH2:29]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[F:16][C:13]1[CH:14]=[N:15][C:7]([O:6][C:5]2[CH:17]=[CH:18][CH:19]=[C:3]([S:2][CH3:1])[CH:4]=2)=[C:8]([CH:12]=1)[C:9]([NH:27][C@H:28]1[CH2:33][CH2:32][CH2:31][C@H:30]([OH:34])[CH2:29]1)=[O:11]

Komponenten

7

Edukt 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 113918232-[3-(Methylsulfanyl)phenoxy]-5-fluoronicotinic acidHCID 117882853-Aminocyclohexanol, (1S,3S)-

Produkt 1

HCID 587461885-fluoro-N-[(1S,3S)-3-hydroxycyclohexyl]-2-[3-(methylsulfanyl)phenoxy]nicotinamideAusbeute 45,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

2-[3-(Methylsulfanyl)phenoxy]-5-fluoronicotinic acid (345 mg, 1.26 mmol) was dissolved in dimethylformamide (10 ml) and triethylamine (865 μl, 11.8 mmol) was added followed by (1S,3S)-3-aminocyclohexanol hydroformate (200 mg, 1.24 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (715 mg, 3.73 mmol) and 1-hydroxybenzotriazole (185 mg, 1.37 mmol). The reaction was stirred under nitrogen at room temperature for 18 h and the solvent was removed under reduced pressure. The residue was partitioned between 10% aq. citric acid solution (50 ml) and diethyl ether (50 ml). The organic was washed with sat. sodium bicarbonate solution (50 ml), water (25 ml) and brine (10 ml), dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography using ethyl acetate:cyclohexane (10:90 to 70:30) as eluant to give 5-fluoro-N-[(1S,3S)-3-hydroxycyclohexyl]-2-[3-(methylsulfanyl)phenoxy]nicotinamide (212 mg) as a colourless gum.

Aufarbeitung

  1. customthe solvent was removed under reduced pressure
  2. customThe residue was partitioned between 10% aq. citric acid solution (50 ml) and diethyl ether (50 ml)
  3. washThe organic was washed with sat. sodium bicarbonate solution (50 ml), water (25 ml) and brine (10 ml)
  4. dry with materialdried over MgSO4
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was purified by flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-ec60d81c44fa4976997189696ebb1fdd
Quelldatensatz
uspto-grants-2006_11
Patentnummer
US07141586B2

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