Potassium Carbonate → HCID 18321823, compound

HRID 613637Notes

Reaction equation

HRID 613637 reaction equation
[C:1]([NH:4][C:5]1[N:10]=[CH:9][C:8](/[CH:11]=[CH:12]/[C:13]([NH:15][CH2:16][C:17]2[S:18][CH:19]=[CH:20][C:21]=2[C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[C:24]([CH2:29][OH:30])[C:23]=2[CH3:31])=[O:14])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].CS(Cl)(=O)=O.C(NC1N=CC(/C=C/C(NCC2SC=CC=2C2C=CC(C)=C(CCl)C=2C)=O)=CC=1)(=O)C.O[C:69]1[CH:70]=[CH:71][CH:72]=[C:73]2[C:78]=1[N:77]=[C:76]([CH3:79])[CH:75]=[CH:74]2.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O.C(N(CC)CC)C>[C:1]([NH:4][C:5]1[N:10]=[CH:9][C:8](/[CH:11]=[CH:12]/[C:13]([NH:15][CH2:16][C:17]2[S:18][CH:19]=[CH:20][C:21]=2[C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[C:24]([CH2:29][O:30][C:69]3[CH:70]=[CH:71][CH:72]=[C:73]4[C:78]=3[N:77]=[C:76]([CH3:79])[CH:75]=[CH:74]4)[C:23]=2[CH3:31])=[O:14])=[CH:7][CH:6]=1)(=[O:3])[CH3:2]

Participants

9

Reactant 5

HCID 11430Potassium CarbonateHCID 132242-Methyl-8-hydroxyquinolineHCID 31297Methanesulfonyl chlorideHCID 18321839HCID 18321839, compoundHCID 18321957HCID 18321957, compound

Product 1

HCID 18321823HCID 18321823, compoundYield 48.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent3×HCID 8471TriethylamineSolvent

Procedure

To a mixture of 2-[(E)-3-(6-acetamidopyridin-3-yl)acryloylaminomethyl]-3-(2,4-dimethyl-3-hydroxymethylphenyl)thiophene (45 mg) and triethylamine (13.6 mg) in N,N-dimethylformamide (2 ml) was added methanesulfonyl chloride (14.2 mg) under ice-cooling, and the mixture was stirred for 1 hour at the same temperature and for 5 hours at ambient temperature. The mixture was poured into water and extracted with chloroform. The organic layer was washed with water and brine, dried over magnesium sulfate and evaporated in vacuo to give a residue containing 2-[(E)-3-(6-Acetamidopyridin-3-yl)acryloylaminomethyl]-3-(2,4-dimethyl-3-chloromethylphenyl)thiophene. To a mixture of 8-hydroxy-2-methylquinoline (14.8 mg) and potassium carbonate (39 mg) in N,N-dimethylformamide (0.5 ml) was added a solution of the residue obtained above in N,N-dimethylformamide (1.5 ml) at ambient temperature, and the mixture was stirred for 6 hours at 50° C. The mixture was poured into water and extracted with chloroform. The organic layer was washed with water and brine, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by preparative thin layer chromatography (chloroform:methanol=20:1, V/V) to give 2-[(E)-3-(6-acetamidopyridin-3-yl)acryloylaminomethyl]-3-[2,4-dimethyl-3-(2-methylquinolin-8-yloxymethyl)phenyl]thiophene (26 mg) as amorphous powder.

Workup

  1. temperaturecooling
  2. extractionextracted with chloroform
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated in vacuo
  6. customto give a residue
  7. additionwas added a solution of the residue
  8. stirringthe mixture was stirred for 6 hours at 50° C
  9. extractionextracted with chloroform
  10. washThe organic layer was washed with water and brine
  11. dry with materialdried over magnesium sulfate
  12. customevaporated in vacuo
  13. customThe residue was purified by preparative thin layer chromatography (chloroform:methanol=20:1, V/V)

Sources & evidence

ORD record
ord-d27c3cd349044689a6c9eb8ba241f4a2
Source dataset
uspto-grants-1999_12
Patent number
US06008229

Reaction notes

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