3-Aminopiperidine-2,6-dione hydrochloride → 2-(2,6-Dioxo-piperidin-3-yl)-4-(3-methoxy-phenylamino)-isoindole-1,3-dione

HRID 448411노트

반응식

HRID 448411 반응식
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:9][C:10]2[CH:18]=[CH:17][CH:16]=[C:12]([C:13]([OH:15])=O)[C:11]=2[C:19]([OH:21])=O)[CH:6]=[CH:7][CH:8]=1.Cl.[NH2:23][CH:24]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:25]1=[O:26]>N1C=CC=CC=1>[O:26]=[C:25]1[CH:24]([N:23]2[C:19](=[O:21])[C:11]3[C:12](=[CH:16][CH:17]=[CH:18][C:10]=3[NH:9][C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=3)[C:13]2=[O:15])[CH2:30][CH2:29][C:28](=[O:31])[NH:27]1

참가 물질

4

반응물 2

HCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 58307244HCID 58307244, 화합물

생성물 1

HCID 588272712-(2,6-Dioxo-piperidin-3-yl)-4-(3-methoxy-phenylamino)-isoindole-1,3-dione수율 76.7%

시약·촉매·용매 1

HCID 1049Pyridine용매

실험 절차

A mixture of 3-(3-methoxy-phenylamino)-phthalic acid (0.32 g, 1.1 mmol) and rac-α-aminoglutarimide hydrochloride (0.18 g, 1.1 mmol) in pyridine (10 mL) was heated to reflux for 15 hours. The reaction mixture was cooled, and the solvent was evaporated in vacuo. The residue was suspended in ethyl acetate (100 mL) and washed with dilute aqueous HCl (2×100 mL) and water (2×100 mL). Solvent was evaporated in vacuo. The residue was purified by ISCO silica gel flash chromatography using a methanol-methylene chloride gradient, eluting the product at 5:95 methanol-methylene chloride to give the title product (0.32 g, 76% yield): mp 210-212° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 mL/min, 240 nm, 60/40 CH3CN/0.1% H3PO4, 2.70 (97.39%); 1H NMR (DMSO-d6) δ 2.04-2.08 (m, 1H), 2.49-2.64 (m, 2H), 2.84-2.94 (m, 1H), 3.75 (s, 3H), 5.13 (dd, J=12.6 Hz, J=5.4 Hz, 1H), 6.71 (dd, J=8.4 Hz, J=2.2 Hz, 1H), 6.90-6.92 (m, 2H), 7.25-7.32 (m, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.60-7.66 (m, 1H), 8.42 (s, 1H), 11.14 (s, 1H); 13C NMR (DMSO-d6) δ 22.1, 31.0, 48.7, 55.1, 107.3, 109.6, 112.2, 113.6, 119.9, 130.2, 132.5, 136.2, 140.7, 142.6, 160.2, 167.0, 168.2, 170.0, 172.8; Anal. calcd for C20H17N3O5: C, 63.32; H, 4.52; N, 11.08. Found: C, 63.22; H, 4.51; N, 10.78.

후처리

  1. temperaturewas heated
  2. temperatureto reflux for 15 hours
  3. temperatureThe reaction mixture was cooled
  4. customthe solvent was evaporated in vacuo
  5. washwashed with dilute aqueous HCl (2×100 mL) and water (2×100 mL)
  6. customSolvent was evaporated in vacuo
  7. customThe residue was purified by ISCO silica gel flash chromatography
  8. washeluting the product at 5:95 methanol-methylene chloride

출처 및 근거

ORD 기록
ord-4f108d453da6468c873951de43837489
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481568B2

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