Aminoacetaldehyde → 3-[[5-Chloro-4-(2,3-dihydro-2-oxo-1H-imidazol-1-yl)-2-methoxyphenyl]-methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3H)-one

HRID 362460

Reaktionsgleichung

Reaktionsgleichung von HRID 362460
[NH2:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([CH2:9][N:10]2[N:14]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=3)[O:12][C:11]2=[O:25])=[C:4]([O:26][CH3:27])[CH:3]=1.[CH2:28]([N:30]([CH2:33]C)CC)[CH3:29].C(Cl)(Cl)=[O:36].NCC=O.[K+].[Br-]>C1COCC1.C1(C)C=CC=CC=1.C(OCC)C.ClCCl>[Cl:8][C:7]1[C:2]([N:1]2[CH:29]=[CH:28][NH:30][C:33]2=[O:36])=[CH:3][C:4]([O:26][CH3:27])=[C:5]([CH2:9][N:10]2[N:14]=[C:13]([C:15]3[CH:16]=[CH:17][C:18]([C:21]([F:22])([F:24])[F:23])=[CH:19][CH:20]=3)[O:12][C:11]2=[O:25])[CH:6]=1

Komponenten

10

Edukt 5

HCID 363AminoacetaldehydeHCID 6371PhosgeneHCID 8471TriethylamineHCID 253877Potassium BromideHCID 161056143-[(4-Amino-5-chloro-2-methoxyphenyl)methyl]-5-[4-(trifluoromethyl) phenyl]-1,3,4-oxadiazol-2(3H)-one

Produkt 1

HCID 158387823-[[5-Chloro-4-(2,3-dihydro-2-oxo-1H-imidazol-1-yl)-2-methoxyphenyl]-methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3H)-one

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 1140TolueneLösungsmittelHCID 3283Diethyl EtherLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
24 °C

Versuchsvorschrift

3-[(4-Amino-5-chloro-2-methoxyphenyl)methyl]-5-[4-(trifluoromethyl) phenyl]-1,3,4-oxadiazol-2(3H)-one (1.14 g, 2.9 mmol) and triethylamine (1.0 ml, 6.8 mmol) were taken up in anhydrous THF (20 ml) and transferred dropwise by cannula into a 20% solution of phosgene in toluene at 0° C. under N2. The reaction was stirred 2.5 h at 24° C., diluted with diethylether (1 vol), and filtered through a celite plug. Concentrated by rotary evaporation to gave a solid which was dissolved in dichloromethane (50 ml) under N2 and aminoacetaldehyde (0.42 ml, 2.9 mmol) was added. The solution was stirred 3 h and concentrated to remove solvent. The residue was taken up in 25 ml of formic acid (88%) and stirred 18 h at 24° C. The formic acid was removed by rotary evaporation the residue taken up in ethyl acetate, washed with saturated NaHCO3 solution and brine, and dried. Concentration on SiO2, and elution with 45% THF/benzene gave 850 mg (65%). mp 201°-202° C.; IR(KBr, ν=cm-1) 3414, 1792, 1694, 1330, 1236, 1136; 1H NMR (300 MHz, CDCl3) δ3.86 (3H, s), 4.97 (2H, s), 6.38 (2H, br, s), 6.99 (1H, s), 7.40 (1H, s), 7.71 (2H, d, J=8.4 Hz), 7.94 (2H, d, J=8.2 Hz), 10.28 (1H, br, s); MS(ESI)m/z: 465 (M--H-)

Aufarbeitung

  1. filtrationfiltered through a celite plug
  2. concentrationConcentrated by rotary evaporation
  3. customto gave a solid which
  4. stirringThe solution was stirred 3 h
  5. concentrationconcentrated
  6. customto remove solvent
  7. stirringstirred 18 h at 24° C
  8. customThe formic acid was removed by rotary evaporation the residue
  9. washwashed with saturated NaHCO3 solution and brine
  10. customdried
  11. concentrationConcentration
  12. washon SiO2, and elution with 45% THF/benzene
  13. customgave 850 mg (65%)

Quellen und Nachweise

ORD-Eintrag
ord-71a76c14311e4eaca5a077c194dd92a8
Quelldatensatz
uspto-grants-1999_02
Patentnummer
US05869509

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