p-Toluenesulfonic acid → [Rac]-2-[1-methyl-3-oxo-3-phenyl-(z)-propenylamino]-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionic acid ethyl ester

HRID 479175Notes

Reaction equation

HRID 479175 reaction equation
[CH2:1]([O:3][C:4](=[O:32])[CH:5]([NH2:31])[CH2:6][C:7]1[C:12]2[S:13][CH:14]=[CH:15][C:11]=2[C:10]([O:16][CH2:17][CH2:18][C:19]2[N:20]=[C:21]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[O:22][C:23]=2[CH3:24])=[CH:9][CH:8]=1)[CH3:2].BrCC1C2SC=CC=2C(OCCC2N=C(C3C=CC=CC=3)OC=2C)=CC=1.C(OC(=O)CN=C(C1C=CC=CC=1)C1C=CC=CC=1)C.[C:79]([CH2:87][C:88](=O)[CH3:89])(=[O:86])[C:80]1[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=1.C(N(CC)CC)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:32])[CH:5]([NH:31]/[C:88](/[CH3:89])=[CH:87]\[C:79](=[O:86])[C:80]1[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=1)[CH2:6][C:7]1[C:12]2[S:13][CH:14]=[CH:15][C:11]=2[C:10]([O:16][CH2:17][CH2:18][C:19]2[N:20]=[C:21]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[O:22][C:23]=2[CH3:24])=[CH:9][CH:8]=1)[CH3:2]

Participants

8

Reactant 6

HCID 6101p-Toluenesulfonic acidHCID 7166BenzoylacetoneHCID 8471TriethylamineHCID 319508Ethyl 2-(diphenylmethyleneamino)acetateHCID 114417504-[2-(7-Bromomethyl-benzo[b]thiophen-4-yloxy)-ethyl]-5-methyl-2-phenyl-oxazoleHCID 69556623[Rac]-2-amino-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionic acid ethyl ester

Product 1

HCID 69557618[Rac]-2-[1-methyl-3-oxo-3-phenyl-(z)-propenylamino]-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionic acid ethyl esterYield 85.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

0.334 g (0.75 mmol) [rac]-2-Amino-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionic acid ethyl ester (prepared from 4-[2-(7-bromomethyl-benzo[b]thiophen-4-yloxy)-ethyl]-5-methyl-2-phenyl-oxazole [PCT Int. Appl. (2001) WO01/79202] and N-(diphenylmethylene)glycine ethyl ester in analogy to the sequence described in examples 15 a] and 15 b]) and 0.161 g (0.97 mmol) benzoylacetone were dissolved in 25 ml of toluene. Then, 0.21 ml (1.5 mmol) triethylamine and 0.026 g (0.15 mmol) 4-toluene sulfonic acid were added and the reaction mixture was heated at reflux for 2 hours. After removing the solvent under reduced pressure, the residue was diluted in water/sodium hydrogen carbonate solution and the reaction mixture was extracted with dichloromethane. The combined organic phases were dried over MgSO4 and evaporated. Purification of the residue by flash-chromatography (silica gel, eluent: gradient of hexane and ethyl acetate) gave 0.38 g (85%) [rac]-2-[1-methyl-3-oxo-3-phenyl-(Z)-propenylamino]-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionic acid ethyl ester as light yellow oil.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 2 hours
  3. customAfter removing the solvent under reduced pressure
  4. additionthe residue was diluted in water/sodium hydrogen carbonate solution
  5. extractionthe reaction mixture was extracted with dichloromethane
  6. dry with materialThe combined organic phases were dried over MgSO4
  7. customevaporated
  8. customPurification of the residue by flash-chromatography (silica gel, eluent: gradient of hexane and ethyl acetate)

Sources & evidence

ORD record
ord-0e3d3846d58b405cb6a2fd76ec7d928c
Source dataset
uspto-grants-2003_11
Patent number
US06642389B2

Reaction notes

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