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

HRID 1053786ノート

反応式

HRID 1053786 の反応式
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

参加物

8

反応物 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 21956832RP-101124HCID 178455121HCID 178455121、化合物HCID 178458475HCID 178458475、化合物

生成物 1

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

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
85 °C

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-129eda5a39b34432ae69f8505ee08331
出典データセット
uspto-grants-2016_07
特許番号
US09394264B2

反応ノート

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