1-Hydroxybenzotriazole → 2-(4,5-dimethyl-furan-2-yl)-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-acetamide

HRID 448488노트

반응식

HRID 448488 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.[OH:34]N1C2C=CC=CC=2N=N1.[CH3:44][C:45]1[CH:46]=C(C(O)=O)[O:48][C:49]=1[CH3:50].Cl.CN(C)[CH2:57][CH2:58][CH2:59]N=C=NCC>C(#N)C>[CH3:46][C:45]1[CH:44]=[C:59]([CH2:58][C:57]([NH:2][CH2:3][C:4]2[CH:12]=[CH:11][CH:10]=[C:9]3[C:5]=2[C:6](=[O:22])[N:7]([CH:14]2[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]2=[O:21])[C:8]3=[O:13])=[O:34])[O:48][C:49]=1[CH3:50]

참가 물질

7

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27749244,5-Dimethylfuran-2-carboxylic acidHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

생성물 1

HCID 672288652-(4,5-dimethyl-furan-2-yl)-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-acetamide수율 72%

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 (0.8 g, 5.4 mmol). After stirring for 10 minutes, 1-hydroxybenzotriazole (0.4 g, 2.6 mmol) and 4,5-dimethyl-2-furoic acid (0.3 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 and was concentrated in vacuo. The residue was dissolved in CH2Cl2 (80 mL), washed with water (40 mL), 1NHCl (2×30 mL), water (40 mL), and brine (40 mL), and dried over MgSO4. Solvent was removed in vacuo, and the residue was purified by ISCO silica gel flash chromatography (Eluent: EtOAc: CH2Cl2 3:7) to afford 2-(4,5-dimethyl-furan-2-yl)-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-acetamide (0.6 g, 72%) as a white solid: mp 221-223° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=2.85 min. (99%); 1H NMR (DMSO-d6) δ 1.95 (s, 3H), 2.05-2.11 (m, 1H), 2.26 (s, 3H), 2.52-2.64 (m, 2H), 2.85-2.97 (m, 1H), 4.86 (d, J=6.0 Hz, 2H), 5.13-5.19 (dd, J=5.3 and 12.6 Hz, 1H), 6.95 (s, 1H), 7.65-7.85 (m, 3H), 8.81 (t, J=6.0 Hz, 1H), 11.14 (s, 1H); 13C NMR (DMSO-d6) δ 9.41, 11.41, 21.96, 30.91, 37.55, 48.84, 116.30, 117.01, 121.80, 127.01, 131.48, 132.88, 134.76, 139.33, 144.63, 150.08, 158.18, 166.95, 167.52, 169.81, 172.74; Anal. Calcd. for C21H19N3O6: C, 61.61; H, 4.68; N, 10.36. Found: C, 61.63; H, 4.43; N, 10.03.

후처리

  1. stirringThe mixture was stirred at room temperature overnight
  2. concentrationwas concentrated in vacuo
  3. dissolutionThe residue was dissolved in CH2Cl2 (80 mL)
  4. washwashed with water (40 mL), 1NHCl (2×30 mL), water (40 mL), and brine (40 mL)
  5. dry with materialdried over MgSO4
  6. customSolvent was removed in vacuo
  7. customthe residue was purified by ISCO silica gel flash chromatography (Eluent: EtOAc: CH2Cl2 3:7)

출처 및 근거

ORD 기록
ord-52e8ecda9a4d4de1a8e6621f2f0812d9
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481568B2

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