Diisopropylethylamine → 1-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-3-(3-methoxy-phenyl)-urea

HRID 331657

반응식

HRID 331657 반응식
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[N:8]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:7]2=[O:22].[CH3:23][O:24][C:25]1[CH:26]=[C:27]([N:31]=[C:32]=[O:33])[CH:28]=[CH:29][CH:30]=1.CCN(C(C)C)C(C)C>C1COCC1>[O:21]=[C:15]1[CH:14]([N:8]2[C:7](=[O:22])[C:6]3[C:10](=[CH:11][CH:12]=[C:4]([CH2:3][NH:2][C:32]([NH:31][C:27]4[CH:28]=[CH:29][CH:30]=[C:25]([O:24][CH3:23])[CH:26]=4)=[O:33])[CH:5]=3)[C:9]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 878433-Methoxyphenyl isocyanateHCID 670197065-(Aminomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione hydrochloride

생성물 1

HCID 577304861-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-3-(3-methoxy-phenyl)-urea수율 6.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
40 °C

실험 절차

To a stirred mixture of 5-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.97 g, 3.00 mmol) and 3-methoxyphenylisocyanate (0.45 g, 3.30 mmol) in THF (20 mL), was added DIPEA (1.05 mL, 6.00 mmol) at room temperature under nitrogen. The mixture was heated to 40° C. for 18 h then cooled to rt. The solvent was removed in vacuo and the residue was dissolved in EtOAc (100 mL). The organic layer was washed with dil. aq. HCl (2×150 mL), water (100 mL), dried (MgSO4) and then concentrated. The residue was triturated in Et2O (50 mL) for 3 h at rt, then refluxed in acetone (50 mL) for 1 h. The product was isolated by filtration and dried in vacuo to give 1-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-3-(3-methoxy-phenyl)-urea as a white solid (0.08 g, 6% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 8.01 min (99.44%); mp: 323-325° C.; 1H NMR (DMSO-d6) δ 2.03-2.09 (m, 1H, CHH), 2.49-2.63 (m, 2H, CHH, CHH), 2.85-2.91 (m, 1H, CHH), 3.70 (s, 3H, CH3), 4.47 (d, J=6.0 Hz, 2H, CH2), 5.15 (dd, J=5.4, 13.5 Hz, 1H, CH), 6.47-6.50 (m, 1H, Ar or NH), 6.82-6.91 (m, 2H, Ar or NH), 7.09-7.15 (m, 2H, Ar or NH), 7.78-7.91 (m, 3H, Ar or NH), 8.74 (s, 1H, NH), 11.12 (s, 1H, NH); 13C NMR (DMSO-d6) δ 21.98, 30.90, 42.57, 48.96, 54.81, 103.52, 106.72, 110.14, 121.63, 123.47, 129.36, 129.65, 131.57, 133.17, 141.49, 143.07, 148.75, 155.16, 159.60, 167.02, 167.18, 169.80, 172.72; LCMS: MH=437; Anal Calcd for C22H20N4O6: C, 58.38; H, 4.85; N, 12.38. Found: C, 58.36; H, 4.45; N, 11.98.

후처리

  1. temperaturethen cooled to rt
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in EtOAc (100 mL)
  4. washThe organic layer was washed with dil. aq. HCl (2×150 mL), water (100 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe residue was triturated in Et2O (50 mL) for 3 h at rt
  8. temperaturerefluxed in acetone (50 mL) for 1 h
  9. customThe product was isolated by filtration
  10. customdried in vacuo

출처 및 근거

ORD 기록
ord-497c8b0ab66a4cdf81464b39c930cb8a
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877780B2

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