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

HRID 1512820Notes

Reaction equation

HRID 1512820 reaction equation
CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[CH3:22][CH:23]([O:25][C:26]1[N:31]=[CH:30][C:29]([C:32]([OH:34])=O)=[CH:28][C:27]=1[O:35][CH3:36])[CH3:24].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>[CH3:24][CH:23]([O:25][C:26]1[N:31]=[CH:30][C:29]([C:32]2[O:34][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:28][C:27]=1[O:35][CH3:36])[CH3:22]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 670254146-[(1-Methylethyl)oxy]-5-(methyloxy)-3-pyridinecarboxylic acidHCID 178506488HCID 178506488, compound

Product 1

HCID 59146075Ethyl 3-(5-{5-[6-[(1-methylethyl)oxy]-5-(methyloxy)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-2-yl)propanoateYield 16.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

EDCI (182 mg) and HOBT (145 mg) were added to a solution of 6-[(1-methylethyl)oxy]-5-(methyloxy)-3-pyridinecarboxylic acid (100 mg) in THF (5 mL). The resulting 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) (196 mg). The resulting mixture was stirred at room temperature for 2 hrs followed by addition of TBAF (495 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-[6-[(1-methylethyl)oxy]-5-(methyloxy)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-2-yl)propanoate (D118) (35 mg). MS (ES): C24H26N4O5 requires 450; found 451.2 (M+H+).

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-d16eaa5acb504cab8f1e11e9049f117e
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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