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

HRID 1053786Notes

Reaction equation

HRID 1053786 reaction equation
C(C1C=C(C=CC=1OC(C)C)C(O)=O)#N.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[Si](OCC1C=C(C=CN=1)C(=N)NO)(C(C)(C)C)(C)C.[Si]([O:56][CH2:57][C:58]1[CH:59]=[C:60]([CH:79]=[CH:80][N:81]=1)[C:61](=[NH:78])[NH:62][O:63][C:64](=O)[C:65]1[CH:70]=[CH:69][C:68]([O:71][CH:72]([CH3:74])[CH3:73])=[C:67]([C:75]#[N:76])[CH:66]=1)(C(C)(C)C)(C)C>CN(C=O)C.CO>[OH:56][CH2:57][C:58]1[CH:59]=[C:60]([C:61]2[N:78]=[C:64]([C:65]3[CH:70]=[CH:69][C:68]([O:71][CH:72]([CH3:74])[CH3:73])=[C:67]([CH:66]=3)[C:75]#[N:76])[O:63][N:62]=2)[CH:79]=[CH:80][N:81]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 21956832RP-101124HCID 178455121HCID 178455121, compoundHCID 178458475HCID 178458475, compound

Product 1

HCID 583550135-(3-(2-(Hydroxymethyl)pyridin-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrileYield 8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

Prepared using General Procedure 2. To a solution of 3-cyano-4-isopropoxybenzoic acid (0.033 g, 0.16 mmol) in DMF (1.0 mL) was added HOBt (0.036 g, 0.23 mmol) and EDC (0.045 g, 0.23 mmol) at room temperature. The reaction was stirred for 0.5 h until the complete formation of the HOBt-acid complex. 2-((Tert-butyldimethylsilyloxy)methyl)-N-hydroxyisonicotinimidamide INT-72 (0.050 g, 0.18 mmol) was added and the mixture was stirred at room temperature for 0.5 h until the formation of the intermediate 2-((tert-butyldimethylsilyloxy)methyl)-N-(3-cyano-4-isopropoxy benzoyloxy) isonicotinimidamide was observed. The reaction mixture was then heated at 85° C. for 4 h. To the cooled reaction mixture MeOH (1.0 mL) was added, and the solution was filtered. The resulting filtrate was purified by preparative HPLC to produce 5.6 mg (8%) of 5-(3-(2-(hydroxymethyl)pyridin-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile 71 as the TFA salt. LCMS-ESI (m/z) calculated for C18H16N4O3: 336.3; found 337.1 [M+H]+, tR=7.45 min (Method 2). 1H NMR (400 MHz, CD3OD) δ 8.78 (d, J=5.5, 1H), 8.48 (dd, J=10.6, 8.3, 1.4, 3H), 8.23 (dd, J=5.5, 1.6, 1H), 7.48 (d, J=9.0, 1H), 4.93 (s, 2H), 4.89 (m, 1H), 1.48 (d, J=6.1, 6H).

Workup

  1. customPrepared
  2. additionwas added
  3. filtrationthe solution was filtered
  4. customThe resulting filtrate was purified by preparative HPLC

Sources & evidence

ORD record
ord-129eda5a39b34432ae69f8505ee08331
Source dataset
uspto-grants-2016_07
Patent number
US09394264B2

Reaction notes

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