三乙胺 → 1-[2-(2,6-Dioxopiperidin-3-YL)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3-naphthalen-2-YL-urea

HRID 448308

反应方程式

HRID 448308 反应方程式
Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][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].[CH:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][C:23]=1[N:32]=[C:33]=[O:34].C(N(CC)CC)C>C1COCC1>[O:21]=[C:15]1[CH:14]([N:7]2[CH2:6][C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:3][NH:2][C:33]([NH:32][C:23]3[CH:24]=[CH:25][C:26]4[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH:22]=3)=[O:34])[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

参与物

5

反应物 3

HCID 8471三乙胺HCID 167182-萘基异氰酸酯HCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

产物 1

HCID 161176161-[2-(2,6-Dioxopiperidin-3-YL)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3-naphthalen-2-YL-urea收率 63.6%

试剂、催化剂与溶剂 1

HCID 8028四氢呋喃溶剂

实验过程

A heterogeneous mixture of 3-(4-aminomethyl-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.50 g, 1.6 mmol), 2-naphthyl isocyanate (0.26 g, 1.6 mmol), and triethylamine (4.9 g, 4.9 mmol) in 25 mL THF was stirred under nitrogen at ambient temperature for 18 hours. The solvent was removed under vacuum. The residue was triturated with 3% aqueous HCl (100 mL) for 1 hour and then filtered, and the filter was washed with additional 3% HCl. The resulting solid was dried, triturated with 30 mL refluxing acetone for 1 hour, and filtered, and the filter was washed with additional hot acetone. The resulting solid was dried and then triturated with 30 mL refluxing acetonitrile, filtered, and dried, to provide 0.45 g of the product in 63% yield: 1H NMR (DMSO-d6) δ 2.01-2.08 (m, 1H), 2.38-2.45 (m, 1H), 2.57-2.65 (m, 1H), 2.86-2.93 (m, 1H), 4.41 (d, J=5.0 Hz, 2H), 4.43 (d, J=17.4 Hz, 1H), 4.57 (d, J=17.4 Hz, 1H), 5.16 (dd, J=13.2 Hz, J=5.1 Hz, 1H), 6.83 (t, J=5.8 Hz, 1H), 7.28-7.79 (m, 9H), 8.02 (d, J=1.8 Hz, 1H), 8.85 (s, 1H), 11.03 (s, 1H); 13C NMR (DMSO-d6) δ 22.6, 31.2, 39.8, 46.2, 51.6, 112.8, 119.6, 121.6, 123.6, 126.2, 126.8, 127.4, 128.2, 128.3, 128.8, 130.4, 131.7, 133.8, 135.6, 138.0, 139.9, 155.3, 168.1, 171.0, 172.8; Anal. calcd for C25H22N4O4.0.2H2O: C, 67.31; H, 5.06; N, 12.56. Found: C, 67.37; H, 4.90; N, 12.53.

后处理

  1. customThe solvent was removed under vacuum
  2. customThe residue was triturated with 3% aqueous HCl (100 mL) for 1 hour
  3. filtrationfiltered
  4. washthe filter was washed with additional 3% HCl
  5. customThe resulting solid was dried
  6. customtriturated with 30 mL
  7. temperaturerefluxing acetone for 1 hour
  8. filtrationfiltered
  9. washthe filter was washed with additional hot acetone
  10. customThe resulting solid was dried
  11. customtriturated with 30 mL
  12. temperaturerefluxing acetonitrile
  13. filtrationfiltered
  14. customdried

来源与证据

ORD记录
ord-5ea8bd162bb740f4acdeac30509837b5
来源数据集
uspto-grants-2013_07
专利号
US08481568B2

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