HCID 178484071, compound → HCID 178484070, compound

HRID 491769Notes

Reaction equation

HRID 491769 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7]2[O:11][C:10]([C:12]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][N:16]=3)=[O:13])=[C:9]([NH:22][C:23]([C@H:25]3[CH2:30][CH2:29][C@H:28]([N:31]([CH3:33])[CH3:32])[CH2:27][CH2:26]3)=[O:24])[C:8]=2[CH:34]=1)(O)=[O:2]>S(Cl)(Cl)=O>[CH3:32][N:31]([CH3:33])[C@H:28]1[CH2:27][CH2:26][C@H:25]([C:23]([NH:22][C:9]2[C:8]3[CH:34]=[C:4]([CH2:1][OH:2])[CH:5]=[CH:6][C:7]=3[O:11][C:10]=2[C:12]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][N:16]=2)=[O:13])=[O:24])[CH2:30][CH2:29]1

Participants

3

Reactant 1

HCID 178484071HCID 178484071, compound

Product 1

HCID 178484070HCID 178484070, compoundYield 19.5%

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Procedure

Trans-5-carboxy-3-[4-(dimethylamino)cyclohexyl-carbonylamino]-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide (243 mg) obtained in Example 78 is suspended in thionyl chloride (2.5 ml), and the mixture is stirred at room temperature for 10 minutes, then stirred at 50° C. for 10 minutes. The mixture is cooled to room temperature and stirred for one hour. The reaction solution is concentrated to dryness under reduced pressure. The resulting residue is suspended in tetrahydrofuran/chloroform (2:1, 15 ml), and thereto is added sodium borohydride (150 mg), and the mixture is stirred at room temperature overnight. To the reaction solution is poured 1N hydrochloric acid under ice-cooling, and the mixture is stirred for 0.5 hour. A saturated aqueous sodium hydrogen carbonate solution is further poured thereto, and the mixture is extracted with chloroform. The organic layer is washed with a saturated aqueous sodium hydrogen carbonate solution and a saturated brine, dried over sodium sulfate, and the solvent is evaporated under reduced pressure. The resulting residue is purified by NH-silica gel column chromatography (eluent: chloroform, then chloroform/methanol=200/1) to give trans-3-[4-(dimethylamino) cyclohexylcarbonylamino]-5-hydroxymethyl-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide (46 mg). This product is dissolved in chloroform (1 ml), and thereto is added 2N hydrogen chloride in methanol (0.1 ml), and the reaction solution is concentrated under reduced pressure. The resulting residue is suspended in ethyl acetate-methanol, and the precipitates are collected by filtration, and dried to give the title compound (45 mg).

Workup

  1. stirringstirred at 50° C. for 10 minutes
  2. temperatureThe mixture is cooled to room temperature
  3. stirringstirred for one hour
  4. concentrationThe reaction solution is concentrated to dryness under reduced pressure
  5. additionis added sodium borohydride (150 mg)
  6. stirringthe mixture is stirred at room temperature overnight
  7. additionTo the reaction solution is poured 1N hydrochloric acid under ice-
  8. temperaturecooling
  9. stirringthe mixture is stirred for 0.5 hour
  10. additionA saturated aqueous sodium hydrogen carbonate solution is further poured
  11. extractionthe mixture is extracted with chloroform
  12. washThe organic layer is washed with a saturated aqueous sodium hydrogen carbonate solution
  13. dry with materiala saturated brine, dried over sodium sulfate
  14. customthe solvent is evaporated under reduced pressure
  15. customThe resulting residue is purified by NH-silica gel column chromatography (eluent

Sources & evidence

ORD record
ord-89f7a5cbf0b14caba3ff7fcdde3d8220
Source dataset
uspto-grants-2009_05
Patent number
US07531537B2

Reaction notes

Loading…