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

HRID 1512844Notes

Reaction equation

HRID 1512844 reaction equation
C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[C:22]([C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:32]=1[O:33][CH:34]([CH3:36])[CH3:35])[C:27]([OH:29])=O)#[N:23].[F:37][C:38]1[C:46](/[C:47](/[NH:50]O)=[N:48]/[H])=[C:45]2[C:41]([C:42]([CH2:52][CH2:53][C:54]([O:56][CH2:57][CH3:58])=[O:55])=[CH:43][NH:44]2)=[CH:40][CH:39]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:22]([C:24]1[CH:25]=[C:26]([C:27]2[O:29][N:48]=[C:47]([C:46]3[C:38]([F:37])=[CH:39][CH:40]=[C:41]4[C:45]=3[NH:44][CH:43]=[C:42]4[CH2:52][CH2:53][C:54]([O:56][CH2:57][CH3:58])=[O:55])[N:50]=2)[CH:30]=[CH:31][C:32]=1[O:33][CH:34]([CH3:36])[CH3:35])#[N:23]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 21956832RP-101124HCID 178506517HCID 178506517, compound

Product 1

HCID 59146092Ethyl 3-[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1H-indol-3-yl]propanoateYield 86.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

HOBT (672 mg) and EDCI (841 mg) were added to a solution of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (450 mg) in THF (10 mL). The resulting solution was stirred for 1 hour. Ethyl 3-{6-fluoro-7-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D145) (836 mg) in THF (5 mL) was added, and the reaction mixture was stirred at RT for 2 hours. TBAF (2.02 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, and dried over anhydrous sodium sulfate. The dried solution was concentrated. The residue was purified by column chromatography to afford ethyl 3-[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1H-indol-3-yl]propanoate (D148) (875 mg) as a yellow solid. MS (ES): C25H23FN4O4 requires 462; found 463.2 (M+H+).

Workup

  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

Sources & evidence

ORD record
ord-b5e0312ee47540dfa8b42f5a60ab97a7
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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