3,4-Dichlorophenyl isocyanate → HCID 16117344, compound

HRID 448294Notes

Reaction equation

HRID 448294 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]=[C:10]=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8].Cl.[NH2:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[CH2:17][N:18]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:19]2=[O:24].C(N(CC)CC)C>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([NH:13][CH2:14][C:15]2[CH:23]=[CH:22][CH:21]=[C:20]3[C:16]=2[CH2:17][N:18]([CH:25]2[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]2=[O:32])[C:19]3=[O:24])=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 3

HCID 76073,4-Dichlorophenyl isocyanateHCID 8471TriethylamineHCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 16117344HCID 16117344, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3,4-Dichlorophenyl isocyanate (0.5 g, 2.7 mmol) was added to a stirred suspension of 3-(4-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.7 g, 2.1 mmol) and triethylamine (0.3 g, 2.9 mmol) in THF (30 mL). The mixture was stirred at room temperature overnight. The mixture was concentrated, and the residue was stirred with 1N HCl (30 mL). The mixture was filtered, and the solid was slurried with hot methanol (20 mL) to give 1-(3,4-dichloro-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-urea (0.6 g, 67%) as a white solid: mp 253-255° C.; 1H NMR (DMSO-d6) δ 2.00-2.05 (m, 1H), 2.37-2.65 (m, 2H), 2.86-3.00 (m, 1H), 4.36-4.58 (m, 4H, 2CH2), 5.11-5.18 (dd, J=4.9 and 13.1 Hz, 1H, CH), 6.89 (t, J=5.6 Hz, 1H, NH), 7.24-7.84 (m, 6H, Ar), 8.96 (s, 1H, NH), 11.01 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.56, 31.17, 39.69, 46.19, 51.58, 117.86, 118.83, 121.58, 122.37, 128.29, 130.38, 130.86, 131.64, 135.27, 139.91, 140.56, 154.87, 168.05, 170.98, 172.81; Anal. calcd. for C21H18N4O4Cl2: C, 54.68; H, 3.93; N, 12.15; Cl, 15.37. Found: C, 54.52; H, 3.78; N, 11.89; Cl, 15.28.

Workup

  1. concentrationThe mixture was concentrated
  2. stirringthe residue was stirred with 1N HCl (30 mL)
  3. filtrationThe mixture was filtered

Sources & evidence

ORD record
ord-16d8328fdec740d7a3d5306f6b8ee061
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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