Cesium carbonate → HCID 23533311, compound

HRID 1795340Notes

Reaction equation

HRID 1795340 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:24][CH3:25])[CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([OH:14])=O)[CH:8]=[C:7]2[O:15][CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21].[N:26]1([C:32]2[CH:37]=[CH:36][C:35]([NH-:38])=[CH:34][CH:33]=2)[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.[CH3:39][N:40]1[CH2:46][CH2:45][CH2:44][NH:43][CH2:42][CH2:41]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:26]1([C:32]2[CH:33]=[CH:34][C:35]([NH:38][C:12]([C:9]3[CH:8]=[C:7]([O:15][CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:6]4[C:11](=[C:2]([N:43]5[CH2:44][CH2:45][CH2:46][N:40]([CH3:39])[CH2:41][CH2:42]5)[CH:3]=[C:4]([O:24][CH3:25])[CH:5]=4)[N:10]=3)=[O:14])=[CH:36][CH:37]=2)[CH2:27][CH2:28][O:29][CH2:30][CH2:31]1

Participants

7

Reactant 5

HCID 10796Cesium carbonateHCID 2283491-MethylhomopiperazineHCID 634876Binap, (A+-)-HCID 22142183HCID 22142183, 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, 1 H, NH), 7.73 (s, 1 H, ArH3), 7.68 (d, 2 H, Jo=8.9 Hz, ArH2′ & H6′), 7.00 (d, 2 H, Jo=8.9 Hz, ArH3′ & H5′), 6.94 (d, 1 H, Jm=2.7 Hz, ArH5), 6.66 (d, 1 H, Jm=2.7 Hz, ArH7), 5.62 (s, 2 H, OCH2O), 3.87 s, 3 H, OCH3), 3.80 (t, 2 H, J=8.0 Hz, OCH2CH2Si), 3.73 (t, 4 H, J=4.7 Hz, OCH2CH2N), 3.63 (t, 2 H, J=5.9 Hz, ArNCH2CH2CH2NCH3), 3.33 (bs, 2 H, ArNCH2CH2NCH3), 3.09 (t, 4 H, J=4.7 Hz, OCH2CH2N), 2.97 (bs, 2 H, ArNCH2CH2NCH3), 2.69 (bs, 2 H, ArNCH2CH2CH2NCH3), 2.35 (s, 3 H, NCH3), 2.09 (bs, 2 H ArNCH2CH2CH2NCH3), 0.94 (t, 2 H, J=8.0 Hz, OCH2CH2Si), −0.03 (s, 9 H, Si(C H3)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-c5c34ddf542f455cafccb7032739d7f8
Source dataset
uspto-grants-2006_04
Patent number
US07026314B2

Reaction notes

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