1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Ethyl 3-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]propanoate

HRID 1512749Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1512749
CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl: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:40]=[CH:41][CH:42]=[C:43]2[C:47]=1[NH:46][CH:45]=[C:44]2[CH2:48][CH2:49][C:50]([O:52][CH2:53][CH3:54])=[O:51].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:22][C:23]1[CH:24]=[C:25]([C:33]2[O:35][N:55]=[C:38]([C:39]3[CH:40]=[CH:41][CH:42]=[C:43]4[C:47]=3[NH:46][CH:45]=[C:44]4[CH2:48][CH2:49][C:50]([O:52][CH2:53][CH3:54])=[O:51])[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 180705825-Chloro-6-isopropoxynicotinic acidHCID 178506492HCID 178506492, Verbindung

Produkt 1

HCID 58222445Ethyl 3-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]propanoateAusbeute 81,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

EDCI (189 mg) and HOBT (162 mg) were added to a solution of 5-chloro-6-[(1-methylethyl)oxy]-3-pyridinecarboxylic acid (105 mg) in THF (2.5 mL), The mixture was stirred at room temperature for 0.5 hour, followed by addition of ethyl 3-{7-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D35) (200 mg) in THF (2.5 mL). The resulting mixture was stirred for 1 hour, followed by addition of TBAF (512 mg). The reaction vessel was sealed and stirred at 120° C. in the microwave for 1.5 hour. THF was removed. The residue was dissolved in EtOAc. The organic solution was washed with saturated aqueous sodium bicarbonate solution. The organic solution was dried over anhydrous sodium sulfate. The dried solution was concentrated. The residue was purified by column chromatography to afford ethyl 3-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]propanoate (D36) (180 mg) as a white solid. δH (DMSO-d6, 400 MHz): 1.16 (3H, t), 1.40 (6H, d), 2.71 (2H, t), 3.03 (2H, t), 4.06 (2H, q), 5.46 (1H, m), 7.22 (1H, t), 7.28 (1H, d), 7.83 (1H, d), 7.94 (1H, d), 8.76 (1H, d), 9.06 (1H, d), 10.91 (1H, s);

Aufarbeitung

  1. stirringThe resulting mixture was stirred for 1 hour
  2. customThe reaction vessel was sealed
  3. stirringstirred at 120° C. in the microwave for 1.5 hour
  4. customTHF was removed
  5. dissolutionThe residue was dissolved in EtOAc
  6. washThe organic solution was washed with saturated aqueous sodium bicarbonate solution
  7. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  8. concentrationThe dried solution was concentrated
  9. customThe residue was purified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-be5a9de6bf44470d986e58752f6a9222
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08217028B2

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