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

HRID 2189785Notes

Reaction equation

HRID 2189785 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:41]=[C:42]2[C:46](=[CH:47][CH:48]=1)[N:45]([CH2:49][CH2:50][C:51]([O:53][CH2:54][CH3:55])=[O:52])[N:44]=[CH:43]2>CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]([C:6]2[O:8][N:38]=[C:39]([C:40]3[CH:41]=[C:42]4[C:46](=[CH:47][CH:48]=3)[N:45]([CH2:49][CH2:50][C:51]([O:53][CH2:54][CH3:55])=[O:52])[N:44]=[CH:43]4)[N:56]=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)carbodiimide2×HCID 757711-HydroxybenzotriazoleHCID 21956832RP-101124HCID 178471847HCID 178471847, compound

Product 1

HCID 59316802Ethyl 3-[5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazol-1-yl]propanoateYield 64.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (can be prepared as described in WO2005/58848) (371 mg, 1.81 mmol), EDAC (547 mg, 2.85 mmol) and HOBt (437 mg, 2.85 mmol) in DMF (5 ml) was left standing at RT for 10 minutes. Added ethyl 3-{5-[(hydroxyamino)(imino)methyl]-1H-indazol-1-yl}propanoate (D52) (500 mg, 1.81 mmol) and left standing overnight at RT. Added EDAC (200 mg, 1.04 mmol) and left standing for 24 hours. The mixture was heated at 80° C. for 2 days, standing at RT each night. The mixture was heated at 80° C. for a further 4 hours. Added EtOAc (50 ml) and washed with water (60 ml), sat. NaHCO3 (60 ml) and water (60 ml). The EtOAc layer was dried (MgSO4) and the solvent evaporated. Triturating with ethanol gave the title compound (523 mg) as a beige solid. MS (ES): C24H23N5O4 requires 445; found (MH+) 446.

Workup

  1. waitwas left
  2. waitstanding overnight at RT
  3. waitstanding for 24 hours
  4. waitstanding at RT each night
  5. temperatureThe mixture was heated at 80° C. for a further 4 hours
  6. washAdded EtOAc (50 ml) and washed with water (60 ml), sat. NaHCO3 (60 ml) and water (60 ml)
  7. dry with materialThe EtOAc layer was dried (MgSO4)
  8. customthe solvent evaporated
  9. customTriturating with ethanol

Sources & evidence

ORD record
ord-3d17080500b04bb1bd94f2f2fabf2d54
Source dataset
uspto-grants-2012_12
Patent number
US08324254B2

Reaction notes

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