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

HRID 448308

Reaction equation

HRID 448308 reaction equation
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

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 167182-Naphthyl isocyanateHCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-5ea8bd162bb740f4acdeac30509837b5
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Linked notes

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