Diisopropylethylamine → 1-(3,4-Methylenedioxyphenyl)-3-[2-(2,6-dioxopiperidin-3-YL)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]urea

HRID 448422Notes

Reaction equation

HRID 448422 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].[CH2:23]1[O:31][C:30]2[CH:29]=[CH:28][C:27]([N:32]=[C:33]=[O:34])=[CH:26][C:25]=2[O:24]1.C(N(C(C)C)CC)(C)C>N1C=CC=CC=1>[CH2:23]1[O:31][C:30]2[CH:29]=[CH:28][C:27]([NH:32][C:33]([NH:2][CH2:3][C:4]3[CH:12]=[CH:11][CH:10]=[C:9]4[C:5]=3[C:6](=[O:22])[N:7]([CH:14]3[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]3=[O:21])[C:8]4=[O:13])=[O:34])=[CH:26][C:25]=2[O:24]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 52232135-Isocyanato-1,3-dioxaindaneHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 588272971-(3,4-Methylenedioxyphenyl)-3-[2-(2,6-dioxopiperidin-3-YL)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]ureaYield 81%

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), 3,4-methylenedioxyphenyl isocyanate (0.25 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 95:5 methylene chloride-methanol, to provide 0.56 g of the product in 81% yield: mp 216-218° C.; 1H NMR (DMSO-d6) δ 2.05-2.09 (m, 1H), 2.50-2.58 (m, 2H), 2.84-2.91 (m, 1H), 4.69 (d, J=5.8 Hz, 2H), 5.16 (dd, J=12.4 Hz, d=5.1 Hz, 1H), 5.93 (s, 2H), 6.67-6.70 (m, 2H), 6.77 (d, J=8.4 Hz, 1H), 7.16 (d, J=1.6 Hz, 1H), 7.75-7.88 (m, 3H), 8.67 (s, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 30.9, 38.7, 48.9, 100.5, 100.6, 108.0, 110.4, 121.8, 127.2, 131.6, 133.6, 134.7, 134.8, 140.3, 141.5, 147.1, 155.3, 167.0, 167.6, 169.8, 172.8; Anal. calcd. for C22H18N4O5: C, 58.67; H, 4.03; N, 12.44. Found: C, 58.35; H, 3.95; N, 12.25.

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 95:5 methylene chloride-methanol

Sources & evidence

ORD record
ord-bcf802998e9843c196e1cf7f7319f118
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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