3-Aminopiperidine-2,6-dione hydrochloride → [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-methyl-carbamic acid t-butyl ester

HRID 240671노트

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HRID 240671 반응식
[C:1]([O:5][C:6]([N:8]([CH2:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:13]([C:14]([OH:16])=O)[C:12]=1[C:20]([OH:22])=O)[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:24][CH:25]1[CH2:31][CH2:30][C:29](=[O:32])[NH:28][C:26]1=[O:27]>N1C=CC=CC=1>[C:1]([O:5][C:6](=[O:7])[N:8]([CH2:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:13]2[C:12]=1[C:20](=[O:22])[N:24]([CH:25]1[CH2:31][CH2:30][C:29](=[O:32])[NH:28][C:26]1=[O:27])[C:14]2=[O:16])[CH3:9])([CH3:2])([CH3:3])[CH3:4]

참가 물질

4

반응물 2

HCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 670196793-[(t-Butoxycarbonyl-methyl-amino)-methyl]phthalic acid

생성물 1

HCID 24755597[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-methyl-carbamic acid t-butyl ester수율 60%

시약·촉매·용매 1

HCID 1049Pyridine용매

실험 절차

A stirred mixture of 3-[(t-butoxycarbonyl-methyl-amino)-methyl]-phthalic acid (2.3 g, 7.1 mmol) from above and α-aminoglutarimide hydrochloride (1.3 g, 7.8 mmol) in pyridine (40 mL) was refluxed for 5 hours. The mixture was cooled and concentrated in vacuo. The residue was dissolved in EtOAc (100 mL) and water (50 mL). The EtOAc solution was separated and washed with water (40 mL), IN citric acid (2×40 mL), water (2×40 mL), and brine (40 mL), and then dried (MgSO4). Solvent was removed in vacuo, and the residue was purified by flash chromatography (SiO2, CH2Cl2: EtOAc 8:2) to give [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-methyl-carbamic acid t-butyl ester (1.7 g, 60%): mp 138-140° C.; 1H NMR (DMSO-d6) δ 11.14 (s, 1H), 7.91-7.81 (m, 2H), 7.57 (b, 1H), 5.19-5.12 (dd, J=5.3 and 12.6 Hz, 1H), 4.85 (s, 2H), 2.97-2.83 (m, 1H), 2.89 (s, 3H), 2.63-2.50 (m, 2H), 2.07-2.03 (m, 1H), 1.44-1.29 (d, 9H); 13CNMR (DMSO-d6) δ 172.70, 169.74, 167.48, 166.87, 154.75, 138.31, 134.99, 132.31, 131.74, 127.42, 121.98, 79.13, 48.86, 47.32, 34.84, 30.90, 27.93, 21.94; Anal. Calcd. for C20H23N3O6: C, 59.84; H, 5.78; N, 10.47. Found: C, 59.51; H, 5.68; N, 10.31.

후처리

  1. temperaturewas refluxed for 5 hours
  2. temperatureThe mixture was cooled
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in EtOAc (100 mL)
  5. customThe EtOAc solution was separated
  6. washwashed with water (40 mL), IN citric acid (2×40 mL)
  7. dry with materialwater (2×40 mL), and brine (40 mL), and then dried (MgSO4)
  8. customSolvent was removed in vacuo
  9. customthe residue was purified by flash chromatography (SiO2, CH2Cl2: EtOAc 8:2)

출처 및 근거

ORD 기록
ord-01403058b3864d85bfd79a45f2402b4e
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08648096B2

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