Cesium carbonate → HCID 10164215, compound

HRID 2414538Notes

Reaction equation

HRID 2414538 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, 1H, C(O)NH), 7.69 (d, 2H, Jo=9.0 Hz, ArH2′ & H6′), 7.58 (s, 1H, ArH3), 7.58 (d, 2H, Jo=9.0 Hz, ArH3′ & H5′), 6.95 (d, 1H, Jm=2.7 Hz, ArH5), 6.76 (d, 1H, Jm=2.7 Hz, ArH7), 3.90 (s, 3H, OCH3), 3.75 (t, 4H, J=4.8 Hz, OCH2CH2N), 3.37 (bs, 4H, ArNCH2CH2N), 3.10 (t, 4H, J=4.8 Hz, OCH2CH2N), 3.01 (s, 6H, N(CH3)2), 2.71 (bs, 4H, ArNCH2CH2N), 2.35 (s, 3H, 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-6f911324f08640a6923c551628eb0763
Source dataset
uspto-grants-2004_11
Patent number
US06812225B2

Reaction notes

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