Reaktion #1182970

Reaktionsgleichung

Sodium hydride

4-amino-8-(cyclopropylmethoxy)-7-methoxyquinolin-2(1H)-one

3,4,5-trichloropyridine

→

8-(cyclopropylmethoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-quinolin-2(1H)-one

Ausbeute 78.5%

Lösungsmittel

DMSO

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwith external cooling (internal temperature kept below 30° C.)
2. 2
   SonstigeThe reaction was quenched with water (40 mL)
3. 3
   FiltrationThe resulting solids were collected by filtration
4. 4
   Sonstigepurified by silica gel chromatography (100:1; dichloromethane/methanol)
5. 5
   Sonstigetriturated with ethyl acetate (300 mL)

Vorschrift

Sodium hydride (60%, 14 g, 350 mmol) was added (caution: H2 gas evolution) to a solution of 4-amino-8-(cyclopropylmethoxy)-7-methoxyquinolin-2(1H)-one (18 g, 69 mmol) and DMSO (200 mL) under N2. After 1 h at room temperature, 3,4,5-trichloropyridine (12.6 g, 69 mmol) was added portionwise with external cooling (internal temperature kept below 30° C.), and the reaction was warmed at 32° C. overnight. The reaction was quenched with water (40 mL) and adjusted to pH=6, with saturated potassium phosphate (KH2PO4). The resulting solids were collected by filtration, purified by silica gel chromatography (100:1; dichloromethane/methanol), and then triturated with ethyl acetate (300 mL) to give 22 g of 8-(cyclopropylmethoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-quinolin-2(1H)-one as a straw yellow solid. MS (ESI): 406.1.

Quelle