Cesium carbonate → (E)-ethyl 3-(5-(benzylthio)-2-((5,6-dichloro-2-methoxypyridin-3-yl)amino)phenyl)acrylate

HRID 1504485Notes

Reaction equation

HRID 1504485 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][C:3]=1/[CH:16]=[CH:17]/[C:18]([O:20][CH2:21][CH3:22])=[O:19].[Cl:23][C:24]1[C:29]([Cl:30])=[CH:28][C:27](I)=[C:26]([O:32][CH3:33])[N:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CCOC(C)=O.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].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>[CH2:9]([S:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:27]2[C:26]([O:32][CH3:33])=[N:25][C:24]([Cl:23])=[C:29]([Cl:30])[CH:28]=2)=[C:3](/[CH:16]=[CH:17]/[C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:4]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 1177371982,3-Dichloro-5-iodo-6-methoxypyridineHCID 117740420(E)-Ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate

Product 1

HCID 117746871(E)-ethyl 3-(5-(benzylthio)-2-((5,6-dichloro-2-methoxypyridin-3-yl)amino)phenyl)acrylateYield 81.3%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A RBF was charged with (E)-ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate (2.0 g, 6.38 mmol)), 2,3-dichloro-5-iodo-6-methoxypyridine (2.327 g, 7.66 mmol)), xantphos (0.185 g, 0.319 mmol)), Pd2(dba)3 (0.146 g, 0.160 mmol)), and cesium carbonate (2.91 g, 8.93 mmol)) were added. A reflux condenser was attached and the flask was heated at 90° C. overnight. The mixture was cooled to RT, diluted with EtOAc, and filtered through celite, with the aid of EtOAc. The filtrate was concentrated and i-PrOH was added. The mixture was heated to 110° C. until all the material dissolved, then the solution was allowed to cool to RT overnight causing a yellow solid to crash out of solution. The solids were filtered and washed with i-PrOH, then dried under a nitrogen blanket to afford (E)-ethyl 3-(5-(benzylthio)-2-((5,6-dichloro-2-methoxypyridin-3-yl)amino)phenyl)acrylate (2.54 g, 5.19 mmol, 81% yield) as a yellow solid. m/z (ESI) 491.1 (M+H)+.

Workup

  1. additionwere added
  2. customA reflux condenser was attached
  3. temperatureThe mixture was cooled to RT
  4. filtrationfiltered through celite, with the aid of EtOAc
  5. concentrationThe filtrate was concentrated
  6. additioni-PrOH was added
  7. temperatureThe mixture was heated to 110° C. until all the material
  8. dissolutiondissolved
  9. temperatureto cool to RT overnight
  10. filtrationThe solids were filtered
  11. washwashed with i-PrOH
  12. customdried under a nitrogen blanket

Sources & evidence

ORD record
ord-7259ca8c4a0d4ce5922e74bf71396776
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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