تفاعل #1269174

معادلة التفاعل

8-bromo-4-dimethylamino-6-methoxy-quinoline-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide

8-Bromo-4-dimethylamino-6-methoxy-quinoline-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide

N-methylpiperazine

BINAP

cesium carbonate

→

desired product

المردود 67.0%

4-Dimethylamino-6-methoxy-8-(4-methyl-piperazin-1-yl)-quinoline-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide

المردود 67.0%

المذيبات

toluene

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe resulting wine colored mixture was heated
2. 2
   درجة الحرارةat reflux under nitrogen for 20 hours
3. 3
   تركيزconcentrated
4. 4
   أخرىThe crude mixture was purified by flash chromatography on silica gel using a gradient of 100:0 to 95:5 methylene chloride

الإجراء التجريبي

To a suspension of 8-bromo-4-dimethylamino-6-methoxy-quinoline-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide (Reference Example 28b) (139.9 mg, 0.288 mmol), N-methylpiperazine (48 μL, 0.43 mmol), and 4 Å sieves in 15 mL anhydrous toluene was added Pd2 (dba)2 (15.3 mg, 16.7 μmol), BINAP (63.0 mg, 0.101 mmol) and cesium carbonate (0.436 g, 1.345 mmol). The resulting wine colored mixture was heated at reflux under nitrogen for 20 hours. The reaction mixture was cooled to room temperature and concentrated. The crude mixture was purified by flash chromatography on silica gel using a gradient of 100:0 to 95:5 methylene chloride:methanol to afford the desired product as a yellow solid (96.9 mg, 67%). 1H NMR (300 MHz, DMSO, d6) δ 10.06 (s, 1 H, C(O)NH), 7.69 (d, 2 H, Jo=9.0 Hz, ArH2′& H6′), 7.58 (s, 1 H, ArH3), 7.58 (d, 2 H, Jo=9.0 Hz, ArH3′& H5′), 6.95 (d, 1 H, Jm=2.7 Hz, ArH5), 6.76 (d, 1 H, Jm=2.7 Hz, ArH7), 3.90 (s, 3 H, OCH3), 3.75 (t, 4 H, J=4.8 Hz, OCH2CH2N), 3.37 (bs, 4 H, ArNCH2CH2N), 3.10 (t, 4 H, J=4.8 Hz, OCH2CH2N), 3.01 (s, 6 H, N(CH3)2), 2.71 (bs, 4 H, ArNCH2CH2N), 2.35 (s, 3 H, R2NCH3); Mass Spec.: calc. for [C28H36N6O3+H]+ Theor. m/z=505; Obs.=505.5.

المصدر