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

HRID 1512816Notes

Reaction equation

HRID 1512816 reaction equation
CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[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].O[NH:38]/[C:39](=[N:56]\[H])/[C:40]1[CH:41]=[C:42]2[C:46](=[CH:47][CH:48]=1)[NH:45][C:44]([CH2:49][CH2:50][C:51]([O:53][CH2:54][CH3:55])=[O:52])=[CH:43]2.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:22]([C:24]1[CH:25]=[C:26]([C:27]2[O:29][N:56]=[C:39]([C:40]3[CH:41]=[C:42]4[C:46](=[CH:47][CH:48]=3)[NH:45][C:44]([CH2:49][CH2:50][C:51]([O:53][CH2:54][CH3:55])=[O:52])=[CH:43]4)[N:38]=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 178506488HCID 178506488, compound

Product 1

HCID 67025243Ethyl 3-[5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-2-yl]propanoateYield 31.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

EDCI (187 mg) and HOBT (149 mg) were added to a solution of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (100 mg) in THF (5 mL). The mixture was stirred at room temperature for 1 hour followed by addition of ethyl 3-{5-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-2-yl}propanoate (D31) (201 mg). The resulting mixture was stirred at room temperature for 2 hrs followed by addition of TBAF (510 mg). The reaction vessel was sealed and heated in Biotage Initiator to 120° C. for 2 hrs. After cooling the reaction, 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-[5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-2-yl]propanoate (D114) (68 mg). The product was directly used in the next step without identification.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 2 hrs
  2. customThe reaction vessel was sealed
  3. temperatureheated in Biotage Initiator to 120° C. for 2 hrs
  4. temperatureAfter cooling
  5. customwas removed
  6. dissolutionThe residue was dissolved in EtOAc
  7. washThe organic solution was washed with saturated aqueous sodium bicarbonate solution
  8. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  9. concentrationThe dried solution was concentrated
  10. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-49a78cead4d74485a14630ef1fcf0008
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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