Cesium carbonate → HCID 69270317, compound

HRID 1181972Notes

Reaction equation

HRID 1181972 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:14]=[C:13]([O:15][CH3:16])[C:12]2[C:7](=[C:8](Br)[CH:9]=[C:10]([F:17])[CH:11]=2)[N:6]=1)=[O:4].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:65][N:66]1[CH2:71][CH2:70][NH:69][CH2:68][CH2:67]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[CH:14]=[C:13]([O:15][CH3:16])[C:12]2[C:7](=[C:8]([N:69]3[CH2:70][CH2:71][N:66]([CH3:65])[CH2:67][CH2:68]3)[CH:9]=[C:10]([F:17])[CH:11]=2)[N:6]=1)=[O:4]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 531671-MethylpiperazineHCID 634876Binap, (A+-)-HCID 53419807Methyl 8-bromo-6-fluoro-4-methoxyquinoline-2-carboxylate

Product 1

HCID 69270317HCID 69270317, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Into a 250 mL, 3 neck round bottom flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet is added 2.1 g (6.68 mmol, 1.0 equiv.) of 8-Bromo-6-fluoro-4-methoxy-quinoline-2-carboxylic acid methyl ester (Reference Example 29a) (122 mg, 0.134 mmol, 0.02 equiv.) of tris dibenzylidineacetone dipalladium, 499 mg (0.802 mmol, 0.12 equiv.) of racemic 2,2′-bis(diphenylphosphino)-1,1′-binapthyl and 1 g of 4 A molecular sieves and 80 mL of dry toluene. To the stirred suspension is then added 736 mg, 815 μL, (7.35 mmol, 1.1 equiv.) of 1-methylpiperazine, followed by 3.05 g (9.35 mmol, 1.4 equiv.) of cesium carbonate. The mixture is then heated to 80° C. for 36 hr. At the end of this time completion was monitored by LC/MS analysis of an aliquot. When the reaction was determined to be complete it was cooled to room temperature then filtered through a plug of celite, with toluene washing to remove solid by products. Purification by flash chromatography using a gradient of 5 to 20% methanol in methylene chloride as eluent yielded 2.0 g, (90%) of the desired product. Mass Spec.: calc. for [C17H20FN3O3+H]+ Theor. m/z=334; Obs.=334.

Workup

  1. customInto a 250 mL, 3 neck round bottom flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet
  2. temperaturewas cooled to room temperature
  3. filtrationthen filtered through a plug of celite, with toluene washing
  4. customto remove solid by products
  5. customPurification by flash chromatography

Sources & evidence

ORD record
ord-32011821d434473394e08d4e9ee68ac4
Source dataset
uspto-grants-2007_10
Patent number
US07285662B2

Reaction notes

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