Cesium carbonate → HCID 10164215, compound

HRID 1825683Notes

Reaction equation

HRID 1825683 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[CH:25]=[C:24]([N:26]([CH3:28])[CH3:27])[C:23]4[C:18](=[C:19](Br)[CH:20]=[C:21]([O:29][CH3:30])[CH:22]=4)[N:17]=3)=[O:15])=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH3:32][N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1>[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[CH:25]=[C:24]([N:26]([CH3:28])[CH3:27])[C:23]4[C:18](=[C:19]([N:36]5[CH2:37][CH2:38][N:33]([CH3:32])[CH2:34][CH2:35]5)[CH:20]=[C:21]([O:29][CH3:30])[CH:22]=4)[N:17]=3)=[O:15])=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 531671-MethylpiperazineHCID 634876Binap, (A+-)-HCID 23533341HCID 23533341, compound

Product 1

HCID 10164215HCID 10164215, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

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.

Workup

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

Sources & evidence

ORD record
ord-4fc34c839342406793ca2e2d03b9e273
Source dataset
uspto-grants-2006_05
Patent number
US07045514B2

Reaction notes

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