Cesium carbonate → HCID 23533311, compound

HRID 2414510Notes

Reaction equation

HRID 2414510 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]([O:26][CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:23]4[C:18](=[C:19](Br)[CH:20]=[C:21]([O:35][CH3:36])[CH:22]=4)[N:17]=3)=[O:15])=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.N1(C2C=CC([NH-])=CC=2)CCOCC1.[CH3:51][N:52]1[CH2:58][CH2:57][CH2:56][NH:55][CH2:54][CH2:53]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]([O:26][CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:23]4[C:18](=[C:19]([N:55]5[CH2:56][CH2:57][CH2:58][N:52]([CH3:51])[CH2:53][CH2:54]5)[CH:20]=[C:21]([O:35][CH3:36])[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

7

Reactant 5

HCID 10796Cesium carbonateHCID 2283491-MethylhomopiperazineHCID 634876Binap, (A+-)-HCID 86587186HCID 86587186, compoundHCID 86587187HCID 86587187, compound

Product 1

HCID 23533311HCID 23533311, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a yellow-green suspension of 8-bromo-6-methoxy-4-(2-trimethylsilanyl-ethoxymethoxy)-quinoline-2-carboxylic acid (Reference Example 27c) (4-morpholin-4-yl-phenyl)-amide (1.155 g, 1.96 mmol), N-methyl homopiperazine (0.39 mL, 3.14 mmol), and 4 Å sieves in 30 mL anhydrous toluene was added Pd2(dba)2 (90.0 mg, 0.098 mmol) and BINAP (0.358 g, 0.58 mmol). The resulting reddish brown mixture became lighter in color upon treatment with cesium carbonate (2.544 g, 7.81 mmol). The reaction mixture was heated at reflux under nitrogen for 17 hours. The clear brown solution was cooled to room temperature, concentrated, and then purified by flash chromatography on silica gel using a slow gradient of 95:5 to 50:50 methylene chloride:methanol to afford the desired product (0.989 g, 81%). 1H NMR (300 MHz, DMSO, d6) δ 9.88 (s, 1H, NH), 7.73 (s, 1H, ArH3), 7.68 (d, 2H, Jo=8.9 Hz, ArH2′ & H6′), 7.00 (d, 2H, Jo=8.9 Hz, ArH3′ & H5′), 6.94 (d, 1H, Jm=2.7 Hz, ArH5), 6.66 (d, 1H, Jm=2.7 Hz, ArH7), 5.62 (s, 2H, OCH2O), 3.87 (s, 3H, OCH3), 3.80 (t, 2H, J=8.0 Hz, OCH2CH2Si), 3.73 (t, 4H, J=4.7 Hz, OCH2CH2N), 3.63 (t, 2H, J=5.9 Hz, ArNCH2CH2CH2NCH3), 3.33 (bs, 2H, ArNCH2CH2NCH3), 3.09 (t, 4H, J=4.7 Hz, OCH2CH2N), 2.97 (bs, 2H, ArNCH2CH2NCH3), 2.69 (bs, 2H, ArNCH2CH2CH2CH3), 2.35 (s, 3H, NCH3), 2.09 (bs, 2H, ArNCH2CH2CH2NCH3), 0.94 (t, 2H, J=8.0 Hz, OCH2CH2Si), −0.03 (s, 9H, Si(CH3)3; Mass Spec.: calc. for [C33H47N5O5Si+H]+ Theor. m/z=622; Obs.=622.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux under nitrogen for 17 hours
  3. concentrationconcentrated
  4. custompurified by flash chromatography on silica gel using a slow gradient of 95:5 to 50:50 methylene chloride

Sources & evidence

ORD record
ord-7fb732540dfb4e5abfd6c2b08e6057a7
Source dataset
uspto-grants-2004_11
Patent number
US06812225B2

Reaction notes

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