1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → ethyl 3-[6-(5-{5-methyl-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]propanoate

HRID 1512813Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1512813
CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[CH3:22][C:23]1[CH:24]=[C:25]([C:33]([OH:35])=O)[CH:26]=[N:27][C:28]=1[O:29][CH:30]([CH3:32])[CH3:31].O[NH:37]/[C:38](=[N:55]\[H])/[C:39]1[CH:47]=[C:46]2[C:42]([C:43]([CH2:48][CH2:49][C:50]([O:52][CH2:53][CH3:54])=[O:51])=[CH:44][NH:45]2)=[CH:41][CH:40]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[CH3:22][C:23]1[CH:24]=[C:25]([C:33]2[O:35][N:55]=[C:38]([C:39]3[CH:47]=[C:46]4[C:42]([C:43]([CH2:48][CH2:49][C:50]([O:52][CH2:53][CH3:54])=[O:51])=[CH:44][NH:45]4)=[CH:41][CH:40]=3)[N:37]=2)[CH:26]=[N:27][C:28]=1[O:29][CH:30]([CH3:31])[CH3:32]

Komponenten

7

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 584180446-Isopropoxy-5-methylnicotinic acidHCID 178506487HCID 178506487, Verbindung

Produkt 1

HCID 59146175ethyl 3-[6-(5-{5-methyl-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]propanoateAusbeute 46,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

EDCI (590 mg) and HOBT (507 mg) were added to a solution of 5-methyl-6-[(1-methylethyl)oxy]-3-pyridinecarboxylic acid (300 mg) in THF (5 mL) at RT. The resulting solution was stirred for 30 mins. Ethyl 3-{6-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D107) (845 mg) in THF (5 mL) was added and the reaction mixture was stirred at RT for 2 hours. TBAF (1.6 g) was then added. The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 120° C. for 2 hours. After cooling, the reaction was quenched with water, and extracted with EtOAc for 3 times. The combined organic solution was washed with brine, dried over anhydrous sodium sulfate. The dried solution was concentrated. The residue was purified by column chromatography (20% EtOAc in hexane) to afford ethyl 3-[6-(5-{5-methyl-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]propanoate (D111) (310 mg) as a pale yellow solid. MS (ES): C24H26N4O4 requires 434; found 435.2 (M+H+).

Aufarbeitung

  1. stirringthe reaction mixture was stirred at RT for 2 hours
  2. customThe reaction vessel was sealed
  3. temperatureheated in Biotage Initiator
  4. customnormal to 120° C.
  5. customfor 2 hours
  6. temperatureAfter cooling
  7. customthe reaction was quenched with water
  8. extractionextracted with EtOAc for 3 times
  9. washThe combined organic solution was washed with brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationThe dried solution was concentrated
  12. customThe residue was purified by column chromatography (20% EtOAc in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-bd98986a36894d4793d9d96326dc6fa1
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08217028B2

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