1-Hydroxybenzotriazole → N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-2-pyridin-4-yl-acetamide

HRID 448486

반응식

HRID 448486 반응식
Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13].N12CCCN=C1CCCCC2.ON1C2C=CC=CC=2N=N1.Cl.[N:45]1[CH:50]=[CH:49][C:48]([CH2:51][C:52](O)=[O:53])=[CH:47][CH:46]=1.Cl.CN(C)CCCN=C=NCC>C(#N)C>[O:21]=[C:15]1[CH:14]([N:7]2[C:6](=[O:22])[C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:3][NH:2][C:52](=[O:53])[CH2:51][C:48]3[CH:49]=[CH:50][N:45]=[CH:46][CH:47]=3)[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

참가 물질

7

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 810974-Pyridineacetic acid hydrochlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

생성물 1

HCID 58307309N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-2-pyridin-4-yl-acetamide수율 50%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.2 mmol) in acetonitrile (60 mL), was added 1,8-diazabicyclo[5,4,0]undec-7-ene (1.2 g, 7.8 mmol). After stirring for 10 minutes, 1-hydroxybenzotriazole (0.4 g, 2.6 mmol) and 4-pyridylacetic acid hydrochloride (0.4 g, 2.4 mmol) were added, followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.6 g, 3.2 mmol). The mixture was stirred at room temperature overnight. Solvent was removed in vacuo, and the residue was purified by ISCO silica gel flash chromatography (Eluent: CH3OH: CH2Cl2 3:97) to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-2-pyridin-4-yl-acetamide (0.4 g, 50%) as white solid: mp 294-296° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=0.87 min. (98%); 1H NMR (DMSO-d6) δ 2.02-2.07 (m, 1H), 2.52-2.96 (m, 2H), 2.84-2.96 (m, 1H), 3.59 (s, 2H), 5.12-5.18 (dd, J=5.2 and 12.7 Hz, 1H), 7.31 (d, J=5.5 Hz, 2H), 7.64-7.70 (m, 1H), 7.79-7.84 (m, 2H), 8.50 (d, J=5.6 Hz, 2H), 8.77 (t, J=5.8 Hz, 1H), 11.14 (s, 1H); 13C NMR (DMSO-d6) δ 21.95, 30.90, 37.91, 41.27, 48.83, 121.96, 124.54, 127.17, 131.53, 133.30, 134.71, 138.88, 144.92, 149.37, 166.88, 167.41, 169.33, 169.78, 172.73; Anal. Calcd. for C21H18N4O5: C, 62.07; H, 4.46; N, 13.79. Found: C, 61.77; H, 4.39; N, 13.59.

후처리

  1. stirringThe mixture was stirred at room temperature overnight
  2. customSolvent was removed in vacuo
  3. customthe residue was purified by ISCO silica gel flash chromatography (Eluent: CH3OH: CH2Cl2 3:97)

출처 및 근거

ORD 기록
ord-9fc0d6eb2d814d73a82329905e26a836
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481568B2

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