Pyridine → HCID 23062668, compound

HRID 491806Notes

Reaction equation

HRID 491806 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.Cl[C:16](Cl)([O:18]C(=O)OC(Cl)(Cl)Cl)Cl.N1C=CC=CC=1.[NH2:33][C:34]1[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[O:36][C:35]=1[C:43]([NH:45][C:46]1[CH:51]=[CH:50][C:49]([Cl:52])=[CH:48][N:47]=1)=[O:44]>ClCCl.O>[C:11]([O:10][C:8]([N:5]1[CH2:4][CH2:3][CH:2]([O:1][C:16]([NH:33][C:34]2[C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=3[O:36][C:35]=2[C:43]([NH:45][C:46]2[CH:51]=[CH:50][C:49]([Cl:52])=[CH:48][N:47]=2)=[O:44])=[O:18])[CH2:7][CH2:6]1)=[O:9])([CH3:14])([CH3:13])[CH3:12]

Participants

7

Reactant 4

HCID 1049Pyridine2×HCID 94429TriphosgeneHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 230625903-amino-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide

Product 1

HCID 23062668HCID 23062668, compoundYield 260%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

t-Butyl 4-hydroxy-1-piperidinecarboxylate (175 mg) and triphosgene (90 mg) are dissolved in dichloromethane (5 ml), and thereto is added pyridine (77 μl) with stirring under ice-cooling. The reaction solution is stirred at room temperature for 3 hours, and then cooled again with ice. To the mixture is added 3-amino-N-(5-chloropyridin-2-yl)-benzofuran-2-carboxamide (250 mg) obtained in Reference Example 74, and the mixture is stirred for several minutes. Pyridine (105 μl) is added to the mixture, and the mixture is stirred at room temperature for 3 hours. The reaction solution is poured into water, and the mixture is extracted with chloroform. The organic layer is washed successively with 5% aqueous citric acid solution, water, 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: n-hexane/ethyl acetate=10/1, then 5/1) to give the title compound (406 mg).

Workup

  1. temperaturecooling
  2. stirringThe reaction solution is stirred at room temperature for 3 hours
  3. temperaturecooled again with ice
  4. customobtained in Reference Example 74
  5. stirringthe mixture is stirred for several minutes
  6. stirringthe mixture is stirred at room temperature for 3 hours
  7. extractionthe mixture is extracted with chloroform
  8. washThe organic layer is washed successively with 5% aqueous citric acid solution, water
  9. dry with materiala saturated aqueous sodium hydrogen carbonate solution and a saturated brine, dried over sodium sulfate
  10. customthe solvent is evaporated under reduced pressure
  11. customThe resulting residue is purified by NH-silica gel column chromatography (eluent

Sources & evidence

ORD record
ord-c3df15887cbe4a7fb05d6a4c04e40fe5
Source dataset
uspto-grants-2009_05
Patent number
US07531537B2

Reaction notes

Loading…