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

HRID 423341Notes

Reaction equation

HRID 423341 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])[C:6]([OH:8])=O)#[N:2].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.O[NH:38][C:39](=[NH:56])[C:40]1[CH:48]=[CH:47][CH:46]=[C:45]2[C:41]=1[CH:42]=[CH:43][N:44]2[CH2:49][CH2:50][C:51]([O:53][CH2:54][CH3:55])=[O:52]>CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]([C:6]2[O:8][N:56]=[C:39]([C:40]3[CH:48]=[CH:47][CH:46]=[C:45]4[C:41]=3[CH:42]=[CH:43][N:44]4[CH2:49][CH2:50][C:51]([O:53][CH2:54][CH3:55])=[O:52])[N:38]=2)[CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])#[N:2]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 21956832RP-101124HCID 178471833HCID 178471833, compound

Product 1

HCID 59318416Ethyl 3-[4-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]propanoateYield 33.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (can be prepared as described in WO2005/58848) (113 mg, 0.55 mmol), EDAC (115 mg, 0.60 mmol) and HOBt (82 mg, 0.60 mmol) were dissolved in DMF (5 ml) and left standing for 15 minutes. Added ethyl 3-{4-[(hydroxyamino)(imino)methyl]-1H-indol-1-yl}propanoate (D57) (150 mg, 0.55 mmol) and stood overnight at RT. Heated solution at 80° C. for 2 hours. LC/MS showed mostly product. After heating for a few more hours there was no change. Added EtOAc (20 ml) and washed with water (30 ml). Washed with saturated sodium hydrogen carbonate (30 ml) and water (2×30 ml). Dried over MgSO4 and evaporated off the solvent to obtain 81 mg of the title compound as a pale brown solid. MS (ES) C25H44N4O4 requires 444; found 445 (MH+).

Workup

  1. waitleft
  2. waitHeated solution at 80° C. for 2 hours
  3. temperatureAfter heating for a few more hours there
  4. washAdded EtOAc (20 ml) and washed with water (30 ml)
  5. washWashed with saturated sodium hydrogen carbonate (30 ml) and water (2×30 ml)
  6. dry with materialDried over MgSO4
  7. customevaporated off the solvent

Sources & evidence

ORD record
ord-15793bb69d9f4092b27f46ad6771d3bb
Source dataset
uspto-grants-2012_01
Patent number
US08101775B2

Reaction notes

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