1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → methyl 3-(7-{5-[3-chloro-4,5-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate

HRID 1512779Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1512779
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([O:14][CH2:15][CH3:16])[C:10]=1[O:11][CH2:12][CH3:13])[C:5]([OH:7])=O.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.O[NH:39]/[C:40](=[N:57]\[H])/[C:41]1[CH:42]=[CH:43][CH:44]=[C:45]2[C:49]=1[NH:48][CH:47]=[C:46]2[CH2:50][CH2:51][C:52]([O:54][CH2:55]C)=[O:53].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:7][N:57]=[C:40]([C:41]3[CH:42]=[CH:43][CH:44]=[C:45]4[C:49]=3[NH:48][CH:47]=[C:46]4[CH2:50][CH2:51][C:52]([O:54][CH3:55])=[O:53])[N:39]=2)[CH:8]=[C:9]([O:14][CH2:15][CH3:16])[C:10]=1[O:11][CH2:12][CH3:13]

Komponenten

7

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 46948803-Chloro-4,5-diethoxybenzoic acidHCID 178506492HCID 178506492, Verbindung

Produkt 1

HCID 59146107methyl 3-(7-{5-[3-chloro-4,5-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoateAusbeute 11,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 3-chloro-4,5-bis(ethyloxy)benzoic acid (D69) (184 mg) in tetrahydrofuran (10 mL) stirred at room temperature was added EDCI (192 mg) and HOBT (153 mg). The reaction mixture was stirred for 2 h, followed by addition of methyl 3-{7-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D35) (131 mg). The reaction mixture was stirred at 60° C. for another 2 h, and then TBAF (523 mg) was added. The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 130° C. for 3 h. After cooling the reaction, the solvent was removed. Water (10 mL) and ethyl acetate (30 mL) was added, the organic layer was separated and the solvent was evaporated off. The residue was purified by Mass Directed Auto Prep to afford methyl 3-(7-{5-[3-chloro-4,5-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate (D70) (25 mg) as a white solid. δH (CDCl3, 400 MHz): 1.46 (3H, t), 1.55 (3H, m), 2.78 (2H, t), 3.18 (2H, t), 3.70 (3H, s), 4.22-4.28 (4H, m), 7.21 (1H, d), 7.29 (1H, t), 7.67 (1H, d), 7.81 (1H, t), 7.93 (1H, d), 8.13 (1H, d), 9.60 (1H, s).

Aufarbeitung

  1. stirringThe reaction mixture was stirred at 60° C. for another 2 h
  2. customThe reaction vessel was sealed
  3. temperatureheated in Biotage Initiator
  4. customnormal to 130° C.
  5. customfor 3 h
  6. temperatureAfter cooling
  7. customthe reaction
  8. customthe solvent was removed
  9. additionWater (10 mL) and ethyl acetate (30 mL) was added
  10. customthe organic layer was separated
  11. customthe solvent was evaporated off
  12. customThe residue was purified by Mass Directed Auto Prep

Quellen und Nachweise

ORD-Eintrag
ord-bde843e1de44407792c89b093cc64001
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08217028B2

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