Cesium carbonate → Ethyl 5-(4-fluorobenzamido)-2-[methyl(quinolin-6-yl)amino]thiazole-4-carboxylate

HRID 512544Notes

Reaction equation

HRID 512544 reaction equation
Br[C:2]1[S:3][C:4]([NH:12][C:13](=[O:21])[C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:70][NH:71][C:72]1[CH:73]=[C:74]2[C:79](=[CH:80][CH:81]=1)[N:78]=[CH:77][CH:76]=[CH:75]2>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:20][C:17]1[CH:18]=[CH:19][C:14]([C:13]([NH:12][C:4]2[S:3][C:2]([N:71]([CH3:70])[C:72]3[CH:73]=[C:74]4[C:79](=[CH:80][CH:81]=3)[N:78]=[CH:77][CH:76]=[CH:75]4)=[N:6][C:5]=2[C:7]([O:9][CH2:10][CH3:11])=[O:8])=[O:21])=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 12765505N-methylquinolin-6-amineHCID 86703378Ethyl 2-bromo-5-(4-fluorobenzamido)-thiazole-4-carboxylate

Product 1

HCID 86703379Ethyl 5-(4-fluorobenzamido)-2-[methyl(quinolin-6-yl)amino]thiazole-4-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of ethyl 2-bromo-5-(4-fluorobenzamido)-thiazole-4-carboxylate (0.2 g, 0.50 mmol) in toluene (10 mL) was added Xantphos (0.061 g, 0.10 mmol) and Pd2(dba)3 (0.048 g, 0.040 mmol) under argon gas. To this suspension, cesium carbonate (0.344 g, 0.90 mmol) and N-methylquinolin-6-amine (0.084 g, 0.53 mmol) were added, and the mixture was heated at 110° C. for 16 h. The reaction mixture was filtered through a bed of Celite, and the celite pad was washed with ethyl acetate (3×5 mL). The filtrate was concentrated, and the crude residue was purified by silica gel column chromatography eluted with 50% EtOAc in hexane to give 0.14 g (58% yiled) of the titled compound.

Workup

  1. filtrationThe reaction mixture was filtered through a bed of Celite
  2. washthe celite pad was washed with ethyl acetate (3×5 mL)
  3. concentrationThe filtrate was concentrated
  4. customthe crude residue was purified by silica gel column chromatography
  5. washeluted with 50% EtOAc in hexane

Sources & evidence

ORD record
ord-60225ea68c3c418a8d6f03ad8992ada3
Source dataset
uspto-grants-2015_08
Patent number
US09102637B2

Reaction notes

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