Tetrahydrofuran → HCID 60169085, compound

HRID 1053280Notes

Reaction equation

HRID 1053280 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([C:13](N(OC)C)=[O:14])=[C:10]([C:19]3[CH:24]=[CH:23][C:22]([S:25](=[O:32])(=[O:31])[N:26]=CN(C)C)=[CH:21][CH:20]=3)[C:9]=2[N:33]([CH3:35])[CH3:34])=[CH:4][CH:3]=1.[CH2:36]1COC[CH2:37]1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:12][C:11]([C:13](=[O:14])[CH2:36][CH3:37])=[C:10]([C:19]3[CH:24]=[CH:23][C:22]([S:25]([NH2:26])(=[O:31])=[O:32])=[CH:21][CH:20]=3)[C:9]=2[N:33]([CH3:34])[CH3:35])=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 86705029HCID 86705029, compound2×

Product 1

HCID 60169085HCID 60169085, compoundYield 64.43%

Conditions

Temperature
72.5 °C

Procedure

Grignard reagent (ethyl magnesium bromide, 0.62 g, 4.66 ml 1M solution in THF, 4.67 mmol) was added drop wise to a stirred solution of 5-(4-chlorophenyl)-4-(dimethylamino)-3-(4-(N-((dimethylamino)methylene)sulfamoyl)phenyl)-N-methoxy-N-methylthiophene-2-carboxamide (compound 34g, 0.5 g, 0.93 mmol) in anhydrous THF (30 ml) at 25° C. The reaction mixture was then heated at about 70 to 75° C. for 2 hr. The progress of the reaction was monitored by TLC. After cooling the reaction mixture to 0° C., the reaction mixture was quenched by addition of saturated solution of ammonium chloride (10 ml). The mixture so obtained was then extracted with ethyl acetate (2×30 ml). The combined organic layer was dried over anhydrous Na2SO4. The solvent was evaporated from the dried organic layer under reduced pressure to obtain a crude product, which was then purified by column chromatography over silica gel (100-200 mesh) using 40% ethyl acetate in hexanes as an eluent to obtain the title compound (0.27 g, 64.43%). The title compound was then purified by preparative HPLC (0.135 g, 32.2%).

Workup

  1. temperatureAfter cooling the reaction mixture to 0° C.
  2. customthe reaction mixture was quenched by addition of saturated solution of ammonium chloride (10 ml)
  3. customThe mixture so obtained
  4. extractionwas then extracted with ethyl acetate (2×30 ml)
  5. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  6. customThe solvent was evaporated from the dried organic layer under reduced pressure
  7. customto obtain a crude product, which
  8. customwas then purified by column chromatography over silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-244d6d85d1b649bba93cd95e5464a4e1
Source dataset
uspto-grants-2016_07
Patent number
US09393247B2

Reaction notes

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