Potassium Hydroxide → (1S,3R)-3-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)cyclopentanecarboxylic acid

HRID 1623369Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1623369
[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5](F)=[N:6][CH:7]=1.[NH2:24][C@@H:25]1[CH2:29][CH2:28][C@H:27]([C:30]([OH:32])=[O:31])[CH2:26]1.[OH-].[K+]>O1CCOCC1>[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5]([NH:24][C@@H:25]2[CH2:29][CH2:28][C@H:27]([C:30]([OH:32])=[O:31])[CH2:26]2)=[N:6][CH:7]=1

Komponenten

5

Edukt 3

HCID 14797Potassium HydroxideHCID 15020343-Aminocyclopentane-1-carboxylic acidHCID 58127193HCID 58127193, Verbindung

Produkt 1

HCID 66936933(1S,3R)-3-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)cyclopentanecarboxylic acidAusbeute 7,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To 5′-chloro-2′-fluoro-N-(3-fluorobenzyl)-2,4′-bipyridin-6-amine (100 mg, 0.301 mmol), was added (1S,3R)-3-aminocyclopentanecarboxylic acid (117 mg, 0.904 mmol), powdered potassium hydroxide (85 mg, 1.507 mmol) and dioxane (1 ml). The reaction mixture was stirred at 100° C. for 18 hr in a sealed vessel and followed by LCMS. The crude reaction mixture was partitioned between 30 mL saturated ammonium chloride and 30 mL ethyl acetate. The organic layer was removed, dried over sodium sulfate, and reduced. This was redissolved in 1.5 mL DMSO, filtered, and purified through prep LC. The product fractions were combined and extracted with 50 mL ethyl acetate, which was dried over sodium sulfate, and concentrated to constant mass. 10 mg of the desired compound was obtained. LCMS (m/z): 441.2 (MH+), retention time=0.68 min. 1H NMR (400 MHz, CHLOROFORM-d, 25° C.) δ ppm 1.59 (m, 2H) 1.83 (m, 2H) 1.99 (m, 1H) 2.72 (m, 1H) 3.40 (br. s., 1H) 3.78 (br. s., 1H) 4.42 (br. s., 1H) 5.48 (br. s., 1H) 6.29 (d, J=8.22 Hz, 1H) 6.50 (s, 1H) 6.80-6.92 (m, 2H) 6.95-7.10 (m, 2H) 7.16-7.25 (m, 1H) 7.38 (t, J=8.02 Hz, 1H) 7.89 (s, 1H).

Aufarbeitung

  1. customThe crude reaction mixture
  2. customwas partitioned between 30 mL saturated ammonium chloride and 30 mL ethyl acetate
  3. customThe organic layer was removed
  4. dry with materialdried over sodium sulfate
  5. dissolutionThis was redissolved in 1.5 mL DMSO
  6. filtrationfiltered
  7. custompurified through prep LC
  8. extractionextracted with 50 mL ethyl acetate, which
  9. dry with materialwas dried over sodium sulfate
  10. concentrationconcentrated to constant mass

Quellen und Nachweise

ORD-Eintrag
ord-0f6cb16f130f47b1bfc62f46a8693d35
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08778951B2

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