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

HRID 1807626노트

반응식

HRID 1807626 반응식
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

참가 물질

8

반응물 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 21956832RP-101124HCID 178455121HCID 178455121, 화합물HCID 178458475HCID 178458475, 화합물

생성물 1

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

시약·촉매·용매 2

HCID 887Methanol용매HCID 6228Dimethylformamide용매

반응 조건

온도
85 °C

실험 절차

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). NMR (400 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).

후처리

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

출처 및 근거

ORD 기록
ord-b20174a042674223810d8476792bd7c5
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08357706B2

반응 노트

불러오는 중…