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

HRID 448426

Reaction equation

HRID 448426 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[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:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][C:24]=1[N:33]=[C:34]=[O:35].C(N(C(C)C)CC)(C)C>N1C=CC=CC=1>[O:21]=[C:15]1[CH:14]([N:7]2[C:6](=[O:22])[C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:3][NH:2][C:34]([NH:33][C:24]3[CH:25]=[CH:26][C:27]4[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH:23]=3)=[O:35])[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

Participants

5

Reactant 3

HCID 167182-Naphthyl isocyanateHCID 81531DiisopropylethylamineHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 588272901-[2-(2,6-Dioxopiperidin-3-YL)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3-naphthalen-2-YL-ureaYield 70%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 4-aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride (0.50 g, 1.6 mmol), 2-naphthyl isocyanate (0.26 g, 1.6 mmol), and diisopropylethylamine (0.40 g, 3.1 mmol) in 10 mL pyridine was warmed to 40° C. with stirring under N2, and the resulting solution was stirred at the same temperature for 2 hours. The mixture was cooled, and the solvent was evaporated under vacuum. The residue was chromatographed, eluting with 96:4 methylene chloride-methanol, to provide 0.46 g of the product in 70% yield: mp 201-203° C.; 1H NMR (DMSO-d6) δ 2.07-2.11 (m, 1H), 2.54-2.66 (m, 2H), 2.85-2.91 (m, 1H), 4.75 (d, J=6.0 Hz, 2H), 5.18 (dd, J=12.6 Hz, d=5.4 Hz, 1H), 6.88 (t, J=6.0 Hz, 1H), 7.28-7.34 (m, 1H), 7.38-7.45 (m, 2H), 7.70-7.88 (m, 6H), 8.05 (d, J=1.6 Hz, 1H), 9.05 (s, 1H), 11.20 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 31.0, 38.8, 48.9, 112.7, 119.4, 121.9, 123.6, 126.2, 126.8, 127.2, 127.4, 128.3, 128.8, 131.7, 133.8, 134.8, 137.9, 140.2, 155.3, 167.0, 167.6, 169.8, 172.8; Anal. calcd. for C25H20N4O5.0.5H2O: C, 64.51; H, 4.54; N, 12.03. Found: C, 64.87; H, 4.88; N, 11.59.

Workup

  1. stirringthe resulting solution was stirred at the same temperature for 2 hours
  2. temperatureThe mixture was cooled
  3. customthe solvent was evaporated under vacuum
  4. customThe residue was chromatographed
  5. washeluting with 96:4 methylene chloride-methanol

Sources & evidence

ORD record
ord-517dc972f18f425aabf50f847d0f9dc3
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Linked notes

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