Reaktion #48956

Reaktionsgleichung

EDC.HCl

HOBt

2-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)acetic acid

2-(4-(3,5-Dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)acetic acid

ammonia

→

2-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)acetamide

Lösungsmittel

pyridine

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto cool to rt
2. 2
   Einengenconcentrated
3. 3
   Sonstigeto remove THF
4. 4
   workup.ADDITION2N HCl was added to pH=3
5. 5
   FiltrationThe precipitate was filtered
6. 6
   Waschenwashed with water
7. 7
   Sonstigedried
8. 8
   TemperaturThe crude product was refluxed in ethyl acetate (20 mg/mL) for 10 min
9. 9
   Sonstigesonicated
10. 10
    Temperaturrefluxed for another 10 min
11. 11
    workup.WAITlet stand overnight
12. 12
    FiltrationFiltration
13. 13
    Sonstigedrying

Vorschrift

EDC.HCl (85.8 mg, 0.37 mmol), HOBt (49.4 mg, 0.37 mmol), and DMAP (cat.) were sequentially added to a solution of 2-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)acetic acid (100 mg, 0.24 mmol, Example 49) and pyridine (10 mL). After 5 min, a saturated solution of ammonia in THF (10 mL) was added, and the reaction was heated at 40° C. overnight. The reaction was allowed to cool to rt, concentrated to remove THF, and then 2N HCl was added to pH=3. The precipitate was filtered, washed with water, and dried. The crude product was refluxed in ethyl acetate (20 mg/mL) for 10 min, sonicated to break up large particles, refluxed for another 10 min, and then let stand overnight. Filtration and drying gave 2-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)acetamide: 1H NMR (400 MHz, DMSO-d6): δ 9.58 (br s, 1H), 8.79 (s, 2H), 7.97 (d, 1H), 7.57 (s, 1H), 7.41 (s, 1H), 7.23 (d, 1H), 4.62 (s, 1H), 4.40 (s, 2H), 3.94 (s, 3H); MS (ESI): 409.8.

Quelle