1,2-Dichloroethane → 5-(3-(Benzofuran-5-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile

HRID 1807620Notes

Reaction equation

HRID 1807620 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].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.O[NH:31][C:32]([C:34]1[CH:35]=[CH:36][C:37]2[O:41][CH:40]=[CH:39][C:38]=2[CH:42]=1)=[NH:33]>CN(C=O)C.C([O-])(O)=O.[Na+]>[O:41]1[C:37]2[CH:36]=[CH:35][C:34]([C:32]3[N:31]=[C:6]([C:5]4[CH:9]=[CH:10][C:11]([O:12][CH:13]([CH3:15])[CH3:14])=[C:3]([CH:4]=4)[C:1]#[N:2])[O:8][N:33]=3)=[CH:42][C:38]=2[CH:39]=[CH:40]1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 21956832RP-101124HCID 178513243HCID 178513243, compound

Product 1

HCID 671963915-(3-(Benzofuran-5-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrileYield 44%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

Prepared using General Procedure 2. A flask containing 3-cyano-4-isopropoxybenzoic acid (147.7 mg, 0.72 mmol), HOBt (143 mg, 0.94 mmol) and EDC (180 mg, 0.94 mmol) in DMF (2.0 mL) was stirred for 0.5 h at room temperature under an atmosphere of N2. A solution of N-hydroxybenzofuran-5-carboximidamide INT-68 (218 mg, 0.79 mmol) in DMF (2.0 mL) was added to the mixture. After 1 h at room temperature, the mixture was stirred at 85° C. overnight. The reaction mixture was diluted with NaHCO3 and extracted with EA. The combined organic extracts were dried over Na2SO4, and concentrated. The resulting crude material was chromatographed (EA/hexanes) to provide 110 mg (44%) of 5-(3-(benzofuran-5-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile 69 as a white solid. LCMS-ESI (m/z) calculated for C20H15N3O3: 345.4; found 346.1 [M+H]+, tR=2.77 min (Method 1). 1H NMR (400 MHz, CDCl3) δ 8.45 (dd, J=4.5, 1.9 Hz, 2H), 8.35 (dd, J=8.9, 2.2 Hz, 1H), 8.12 (dd, J=8.6, 1.7 Hz, 1H), 7.71 (d, J=2.2 Hz, 1H), 7.63 (d, J=8.6 Hz, 1H), 7.13 (d, J=9.0 Hz, 1H), 6.88 (dd, J=2.2, 0.8 Hz, 1H), 4.80 (s, 1H), 1.48 (d, J=6.1 Hz, 61-1).

Workup

  1. customPrepared
  2. waitAfter 1 h at room temperature
  3. stirringthe mixture was stirred at 85° C. overnight
  4. extractionextracted with EA
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. concentrationconcentrated
  7. customThe resulting crude material was chromatographed (EA/hexanes)

Sources & evidence

ORD record
ord-7d25faa3ab4c40d6b484a2759de29be0
Source dataset
uspto-grants-2013_01
Patent number
US08357706B2

Reaction notes

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