1-Hydroxybenzotriazole → HCID 69929472, compound

HRID 1840589Notes

Reaction equation

HRID 1840589 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:19]([OH:21])=O)[CH2:10][O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CO[CH:24](OC)[CH2:25][NH:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH:38]=[CH:37][N:36]=[CH:35]2)=[CH:30][CH:29]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(#N)C>[CH2:12]([O:11][CH2:10][C@@H:9]1[N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH:24]=[CH:25][N:26]([CH2:27][C:28]2[CH:29]=[CH:30][C:31]([N:34]3[CH:38]=[CH:37][N:36]=[CH:35]3)=[CH:32][CH:33]=2)[C:19]1=[O:21])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 90234L-Serine, N-[(1,1-dimethylethoxy)carbonyl]-O-(phenylmethyl)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23447299HCID 23447299, compound

Product 1

HCID 69929472HCID 69929472, compoundYield 47.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of N-tert-butoxycarbonyl-O-benzyl-L-serine (1.48 g) and 2,2-dimethoxyethyl[4-(1H-imidazol-1-yl)benzyl]amine (1.31 g) in acetonitrile (50 ml) were added HOBt (842 mg) and WSC hydrochloride (1.05 g), under ice-cooling, and the mixture was stirred at room temperature for 2 hours. To the mixture was added N, N-dimethylaminopyridine (catalytic amount), and the mixture was stirred overnight. The reaction solution was concentrated, and to the residue were added ethyl acetate and water. The organic layer was separated, washed with saturated brine, dried and concentrated, and the residue was purified with silica gel column chromatography (ethyl acetate methanol=20:1). To the obtained product were added p-toluene sulfonic acid (856 mg) and toluene (60 ml), and the mixture was refluxed for 30 minutes and cooled. To the reaction solution was added ethyl acetate, and the mixture was washed with saturated sodium bicarbonate solution and saturated brine, dried and concentrated. The residue was purified with silica gel column chromatography (ethyl acetate:methanol=20:1) to give amorphous of the title compound (1.14 g).

Workup

  1. temperatureunder ice-cooling
  2. stirringthe mixture was stirred overnight
  3. concentrationThe reaction solution was concentrated
  4. additionto the residue were added ethyl acetate and water
  5. customThe organic layer was separated
  6. washwashed with saturated brine
  7. customdried
  8. concentrationconcentrated
  9. customthe residue was purified with silica gel column chromatography (ethyl acetate methanol=20:1)
  10. additionTo the obtained product were added p-toluene sulfonic acid (856 mg) and toluene (60 ml)
  11. temperaturethe mixture was refluxed for 30 minutes
  12. temperaturecooled
  13. additionTo the reaction solution was added ethyl acetate
  14. washthe mixture was washed with saturated sodium bicarbonate solution and saturated brine
  15. customdried
  16. concentrationconcentrated
  17. customThe residue was purified with silica gel column chromatography (ethyl acetate:methanol=20:1)

Sources & evidence

ORD record
ord-53c3a02c26984983be225b6866732b3b
Source dataset
uspto-grants-2004_01
Patent number
US06680312B2

Reaction notes

Loading…