Reaktion #1567526

Reaktionsgleichung

1-cyclopropyl-2-(5-methyl-1,2,4-oxadiazol-3-yl)propan-2-amine hydrochloride

5-cyclopropyl-4-(1-fluoropropan-2-yloxy)picolinic acid

TBTU

triethylamine

→

5-cyclopropyl-N-(1-cyclopropyl-2-(5-methyl-1,2,4-oxadiazol-3-yl)propan-2-yl)-4-(1-fluoropropan-2-yloxy)picolinamide

Lösungsmittel

ethyl acetate

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe reaction was then stirred at room temperature overnight
2. 2
   Extraktionextracted with a 1M aqueous solution of sodium bicarbonate
3. 3
   SonstigeThe organic phase was collected
4. 4
   Extraktionthe aqueous phase was back-extracted with ethyl acetate
5. 5
   TrocknenCombined organic phases were dried over sodium sulfate
6. 6
   Sonstigeevaporated down to dryness
7. 7
   SonstigeThe crude material was purified by flash chromatography on silica eluting with a gradient of heptane and ethyl acetate
8. 8
   Sonstigeto give
9. 9
   workup.ADDITIONa mixture of epimers
10. 10
    SonstigeThe epimers were then separated by preparative chiral HPLC (Chiralpak AD, isopropanol/heptane)
11. 11
    Sonstigecollected (12.5 mg, 9%)

Vorschrift

To a solution of 5-cyclopropyl-4-(1-fluoropropan-2-yloxy)picolinic acid (enantiomer B) (example 289b, 0.08 g, 334 μmol) in dry DMF (2 ml) was added TBTU (113 mg, 351 μmol) and triethylamine (102 mg, 140 μl, 1.00 mmol). The reaction was stirred at room temperature for 30 minutes followed by addition of 1-cyclopropyl-2-(5-methyl-1,2,4-oxadiazol-3-yl)propan-2-amine hydrochloride (example 66e, 72.8 mg, 334 μmol). The reaction was then stirred at room temperature overnight. The reaction was diluted with ethyl acetate and extracted with a 1M aqueous solution of sodium bicarbonate. The organic phase was collected and the aqueous phase was back-extracted with ethyl acetate. Combined organic phases were dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a gradient of heptane and ethyl acetate to give a mixture of epimers. The epimers were then separated by preparative chiral HPLC (Chiralpak AD, isopropanol/heptane) and the title compound was the first epimer collected (12.5 mg, 9%); MS (ESI, m/z): 403.4 (M+H+).

Quelle