Reaktion #1182949

Reaktionsgleichung

sodium hydride

KH2PO4

4-Amino-8-(cyclopentyloxy)-7-methoxyquinolin-2(1H)-one

sodium hydride

3,4,5-trichloropyridine

3,4,5-trichloropyridine

→

8-(cyclopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one

Lösungsmittel

DMSO

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITAfter 19 h
2. 2
   workup.WAITAfter an additional 4 h
3. 3
   FiltrationThe solids were filtered
4. 4
   Waschenwashed with water (25 mL)
5. 5
   Sonstigepurified by reverse-phase HPLC (3:7→1:0; acetonitrile:water)
6. 6
   SonstigeIn some cases, additional purification by silica gel chromatography (1:0→9:1; dichlormethane:methanol)

Vorschrift

4-Amino-8-(cyclopentyloxy)-7-methoxyquinolin-2(1H)-one (340 mg, 1.24 mmol) was added in 3, portions over 5, minutes to a mixture of sodium hydride (NaH) (110 mg, 60%, 2.75 mmol) and DMSO (4 mL) at room temperature under N2. After 5 min, 3,4,5-trichloropyridine (271 mg, 1.49 mmol) was added. After 19 h, more sodium hydride (100 mg, 60%, 2.5 mmol) was added followed by more 3,4,5-trichloropyridine (250 mg, 1.37 mmol). After an additional 4 h, the reaction was poured into 1M KH2PO4 (75 mL) and stirred for 5 min. The solids were filtered, washed with water (25 mL), and then purified by reverse-phase HPLC (3:7→1:0; acetonitrile:water). In some cases, additional purification by silica gel chromatography (1:0→9:1; dichlormethane:methanol) was needed to give 8-(cyclopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one: 1H NMR (400 MHz, DMSO-d6): δ 9.39 (s, 1H), 8.86 (s, 1H), 8.76 (s, 2H), 7.87 (d, 1H), 7.06 (d, 1H), 4.97 (m, 1H), 4.78 (s, 1H), 3.90 (s, 3H), 1.83-1.48 (m, 8H); MS (ESI): 419.7.

Quelle