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

HRID 1512759Notes

Reaction equation

HRID 1512759 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[CH:46]=[CH:45][C:44](/[C:47](/[NH:50]O)=[N:48]/[H])=[C:43]2[C:39]=1[C:40]([CH2:52][CH2:53][C:54]([O:56][CH2:57][CH3:58])=[O:55])=[CH:41][NH:42]2.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:44]3[CH:45]=[CH:46][C:38]([F:37])=[C:39]4[C:43]=3[NH:42][CH:41]=[C:40]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 178506502HCID 178506502, compound

Product 1

HCID 59146114ethyl 3-[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1H-indol-3-yl]propanoateYield 90.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

HOBT (149 mg) and EDCI (187 mg) were added to a solution of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (100 mg) in THF (4 mL). The resulting solution was stirred for 2 h. Ethyl 3-{4-fluoro-7-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D45) (186 mg) in THF (4 mL) was added. The reaction mixture was stirred at RT overnight. TBAF (612 mg) was then added. The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 120° C. for 2.5 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 (25% EtOAc in hexane) to afford ethyl 3-[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1H-indol-3-yl]propanoate (D47) (203 mg) as a pale yellow solid. MS (ES): C25H23FN4O4 requires 462; found 463.2 (M+H+).

Workup

  1. stirringThe reaction mixture was stirred at RT overnight
  2. customThe reaction vessel was sealed
  3. temperatureheated in Biotage Initiator
  4. customnormal to 120° C.
  5. customfor 2.5 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 (25% EtOAc in hexane)

Sources & evidence

ORD record
ord-a5501f2c097f4e1282add54bc51d6427
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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