1,2-Dichloroethane → Ethyl 4-[4-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]butanoate

HRID 423342Notes

Reaction equation

HRID 423342 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].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.O[NH:31][C:32](=[NH:50])[C:33]1[CH:41]=[CH:40][CH:39]=[C:38]2[C:34]=1[CH:35]=[CH:36][N:37]2[CH2:42][CH2:43][CH2:44][C:45]([O:47][CH2:48][CH3:49])=[O:46]>CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]([C:6]2[O:8][N:50]=[C:32]([C:33]3[CH:41]=[CH:40][CH:39]=[C:38]4[C:34]=3[CH:35]=[CH:36][N:37]4[CH2:42][CH2:43][CH2:44][C:45]([O:47][CH2:48][CH3:49])=[O:46])[N:31]=2)[CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])#[N:2]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 21956832RP-101124HCID 178471588HCID 178471588, compound

Product 1

HCID 59318367Ethyl 4-[4-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]butanoateYield 52.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (can be prepared as described in WO2005/58848) (1.21 g, 5.88 mmol), EDC (1.35 g, 7.05 mmol) and HOBt (1.08 g, 7.05 mmol) in dry DMF (85 ml) was stirred for 20 minutes at RT. Added ethyl 4-{4-[(hydroxyamino)(imino)methyl]-1H-indol-1-yl}butanoate (D59) (1.70 g, 5.88 mmol) and stirred at RT for 1 hour. Heated mixture at 80° C. for 5 hours and left overnight at RT. Heated at 80° C. for 6 hours then evaporated off the DMF. Added EtOAc (200 ml) and washed with sat. NaHCO3 (200 ml) and water (200 ml). Dried over MgSO4 and evaporated off the solvent. Subjected the residue to chromatography using the biotage (EtOAc/hexane 1:2) and evaporated the cleanest fractions to yield 1.42 g the title compound as a white solid. δH (400 MHz, d6-DMSO) 1.15 (3H, t), 1.39 (6H, d), 2.04 (2H, apparent quintet), 2.24 (2H, t), 4.00 (2H, q), 4.31 (2H, t), 4.94-5.04 (1H, m), 7.10 (1H, dd), 7.31 (1H, t), 7.56-7.60 (2H, m), 7.77 (1H, d), 7.95 (1H, d), 8.45 (1H, dd), 8.56 (1H, d). MS (ES) C26H26N4O4 requires 458; found 459 (MH+).

Workup

  1. temperatureHeated mixture at 80° C. for 5 hours
  2. waitleft overnight at RT
  3. temperatureHeated at 80° C. for 6 hours
  4. customthen evaporated off the DMF
  5. washAdded EtOAc (200 ml) and washed with sat. NaHCO3 (200 ml) and water (200 ml)
  6. dry with materialDried over MgSO4
  7. customevaporated off the solvent
  8. customevaporated the cleanest fractions

Sources & evidence

ORD record
ord-75332411ce1146ddbb10e5eefba55d73
Source dataset
uspto-grants-2012_01
Patent number
US08101775B2

Reaction notes

Loading…