1,2-Dichloroethane → n-(2-(5-(3-(2,4-Dihydroxy-5-isopropylphenyl)-5-hydroxy-4h-1,2,4-triazol-4-yl)-1h-indol-1-yl)ethyl)-4-(2,5-dioxo-2,5-dihydro-1h-pyrrol-1-yl)-n-methylbutanamide

HRID 449813Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 449813
[OH:1][C:2]1[N:3]([C:18]2[CH:19]=[C:20]3[C:24](=[CH:25][CH:26]=2)[N:23]([CH2:27][CH2:28][NH:29][CH3:30])[CH:22]=[CH:21]3)[C:4]([C:7]2[CH:12]=[C:11]([CH:13]([CH3:15])[CH3:14])[C:10]([OH:16])=[CH:9][C:8]=2[OH:17])=[N:5][N:6]=1.[O:31]=[C:32]1[CH:36]=[CH:35][C:34](=[O:37])[N:33]1[CH2:38][CH2:39][CH2:40][C:41]([OH:43])=O.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl.CN(C=O)C.O.C(OCC)(=O)C>[OH:17][C:8]1[CH:9]=[C:10]([OH:16])[C:11]([CH:13]([CH3:14])[CH3:15])=[CH:12][C:7]=1[C:4]1[N:3]([C:18]2[CH:19]=[C:20]3[C:24](=[CH:25][CH:26]=2)[N:23]([CH2:27][CH2:28][N:29]([CH3:30])[C:41](=[O:43])[CH2:40][CH2:39][CH2:38][N:33]2[C:34](=[O:37])[CH:35]=[CH:36][C:32]2=[O:31])[CH:22]=[CH:21]3)[C:2]([OH:1])=[N:6][N:5]=1

Komponenten

8

Edukt 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 34049044-Maleimidobutyric AcidHCID 178484195HCID 178484195, Verbindung

Produkt 1

HCID 178438832n-(2-(5-(3-(2,4-Dihydroxy-5-isopropylphenyl)-5-hydroxy-4h-1,2,4-triazol-4-yl)-1h-indol-1-yl)ethyl)-4-(2,5-dioxo-2,5-dihydro-1h-pyrrol-1-yl)-n-methylbutanamideAusbeute 46,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 22350042dichloromethane N,N-dimethylformamideLösungsmittel

Versuchsvorschrift

The benzylether [5-(2,4-bis(benzyloxy)-5-isopropylphenyl)-4-(1-(2-(methylamino)ethyl)-1H-indol-5-yl)-4H-1,2,4-triazol-3-ol; 294 mg, 0.5 mmol) was dissolved in 6 ml degassed ethyl acetate and ethanol (1:1). 50 mg Pd/C (10%) was added and the mixture stirred under hydrogen (balloon) at rt for 6 h. After filtration the solvent was removed and the crude purified by chromatography on silica with DCM/MeOH (5-20%)/NH4OH (0.5%) to yield 203 mg (0.5 mmol) 4-(5-hydroxy-4-(1-(2-(methylamino)ethyl)-1H-indol-5-yl)-4H-1,2,4-triazol-3-yl)-6-isopropylbenzene-1,3-diol. This amine (203 mg) was added to 4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)butanoic acid (110 mg, 0.6 mmol), EDC (154 mg, 0.8 mmol) and HOBt (108 mg, 0.8 mmol) in 9 ml DCM/DMF (2:1) at rt. The mixture was stirred for 12 h and then ethyl acetate and water added. The aq. Phase was extracted twice with ethyl acetate and the combined organic extracts washed with brine and dried over MgSO4. The crude was purified by chromatography on silica with DCM/MeOH (0-8%) to yield 133 mg (0.23 mmol) N-(2-(5-(3-(2,4-dihydroxy-5-isopropylphenyl)-5-hydroxy-4H-1,2,4-triazol-4-yl)-1H-indol-1-yl)ethyl)-4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-methylbutanamide.

Aufarbeitung

  1. extractionThe aq. Phase was extracted twice with ethyl acetate
  2. washthe combined organic extracts washed with brine
  3. dry with materialdried over MgSO4
  4. customThe crude was purified by chromatography on silica with DCM/MeOH (0-8%)

Quellen und Nachweise

ORD-Eintrag
ord-5c4d6b2c1ba74b0ab336edba394f647b
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08486932B2

Notizen zur Reaktion

Wird geladen…