Tetrahydrofuran → HCID 71187164, compound

HRID 1844543Notes

Reaction equation

HRID 1844543 reaction equation
CN(C=[N:5][S:6]([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:20]([O:21][CH3:22])=[CH:19][CH:18]=[C:17]([C:23]3[S:27][C:26]([C:28](N(OC)C)=[O:29])=[CH:25][C:24]=3[CH3:34])[CH:16]=2)=[CH:11][CH:10]=1)(=[O:8])=[O:7])C.[CH2:35]1COC[CH2:36]1>>[CH3:22][O:21][C:20]1[CH:19]=[CH:18][C:17]([C:23]2[S:27][C:26]([C:28](=[O:29])[CH2:35][CH3:36])=[CH:25][C:24]=2[CH3:34])=[CH:16][C:15]=1[C:12]1[CH:11]=[CH:10][C:9]([S:6]([NH2:5])(=[O:8])=[O:7])=[CH:14][CH:13]=1

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 86720680HCID 86720680, compound

Product 1

HCID 71187164HCID 71187164, compound

Conditions

Temperature
82.5 °C

Procedure

Grignard reagent (ethyl magnesium bromide, 1.32 g, 9.9 ml, 9.97 mmol) was added drop wise to a stirred solution of 5-(4′-(N-((dimethylamino)methylene)sulfamoyl)-6-methoxy-[1,1′-biphenyl]-3-yl)-N-methoxy-N,4-dimethylthiophene-2-carboxamide (1d, 1.0 g, 1.99 mmol) in anhydrous THF (20 ml) at 25° C. The reaction mixture was heated at 80-85° C. for 1 hour. The progress of the reaction was monitored by TLC. The reaction mixture was cooled to 0° C. The cooled reaction mixture was then quenched by adding a saturated solution of ammonium chloride (10 ml). The mixture was then extracted with ethyl acetate (3×60 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. The crude product so obtained was purified by flash chromatography using 30-40% ethyl acetate in hexane as an eluent to obtain the title compound. The compound was re-purified by dissolving 0.68 g of the compound in ethyl acetate (5 ml) and precipitating it by slow addition of diisopropyl ether. (0.180 g, 21.7%).

Workup

  1. temperatureThe reaction mixture was cooled to 0° C
  2. customThe cooled reaction mixture
  3. customwas then quenched
  4. additionby adding a saturated solution of ammonium chloride (10 ml)
  5. extractionThe mixture was then extracted with ethyl acetate (3×60 ml)
  6. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  7. customThe solvent was evaporated from the dried organic layer under reduced pressure
  8. customto obtain a crude product
  9. customThe crude product so obtained
  10. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-e76c446ff39343ac9c0bef1922b0dfc6
Source dataset
uspto-grants-2015_02
Patent number
US08946432B2

Reaction notes

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