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

HRID 1512817Notes

Reaction equation

HRID 1512817 reaction equation
CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl:22][C:23]1[CH:24]=[C:25]([C:33]([OH:35])=O)[CH:26]=[N:27][C:28]=1[O:29][CH:30]([CH3:32])[CH3:31].O[NH:37]/[C:38](=[N:55]\[H])/[C:39]1[CH:40]=[C:41]2[C:45](=[CH:46][CH:47]=1)[NH:44][C:43]([CH2:48][CH2:49][C:50]([O:52][CH2:53][CH3:54])=[O:51])=[CH:42]2.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:22][C:23]1[CH:24]=[C:25]([C:33]2[O:35][N:55]=[C:38]([C:39]3[CH:40]=[C:41]4[C:45](=[CH:46][CH:47]=3)[NH:44][C:43]([CH2:48][CH2:49][C:50]([O:52][CH2:53][CH3:54])=[O:51])=[CH:42]4)[N:37]=2)[CH:26]=[N:27][C:28]=1[O:29][CH:30]([CH3:31])[CH3:32]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 180705825-Chloro-6-isopropoxynicotinic acidHCID 178506488HCID 178506488, compound

Product 1

HCID 58222470Ethyl 3-[5-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-2-yl]propanoateYield 49.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

EDCI (92 mg) and HOBT (80 mg) were added to a solution of 5-chloro-6-[(1-methylethyl)oxy]-3-pyridinecarboxylic acid (52 mg) in THF (6 mL). The resulting mixture was stirred for 1 hour followed by addition of ethyl 3-{5-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-2-yl}propanoate (D31) (100 mg). The resulting mixture was stirred for 3 hours followed by addition of TBAF (251 mg). The reaction vessel was sealed, and heated at 120° C. in the microwave for 3 hours. 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-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-2-yl]propanoate (D115) (54 mg). MS (ES): C23H23ClN4O4 requires 454; found 455.2 (M+H+).

Workup

  1. stirringThe resulting mixture was stirred for 3 hours
  2. customThe reaction vessel was sealed
  3. customTHF was removed
  4. dissolutionThe residue was dissolved in EtOAc
  5. washThe organic solution was washed with saturated aqueous sodium bicarbonate solution
  6. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  7. concentrationThe dried solution was concentrated
  8. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-456f2f9eaaa54a6bb44c9bfed6beb2b3
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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