Phenyl isocyanate → HCID 53246788, compound

HRID 448283Notes

Reaction equation

HRID 448283 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].C(N(CC)CC)C.[C:29]1([N:35]=[C:36]=[O:37])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>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:36]([NH:35][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[O:37])[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

Participants

5

Reactant 3

HCID 7672Phenyl isocyanateHCID 8471TriethylamineHCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 53246788HCID 53246788, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
4 °C

Procedure

A 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, 2.7 mmol) in THF (30 mL) was cooled to 4° C. Phenyl isocyanate (0.3 g, 2.7 mmol) was added, and the mixture was stirred at room temperature for 5 hours. The mixture was concentrated, and the residue was stirred with 1N HCl (30 mL). The solid was collected and slurried with ethanol (10 mL) to give 1-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3-phenyl-urea (0.7 g, 89%) as a white solid: mp 328-330° C.; 1H NMR (DMSO-d6) δ 2.00-2.04 (m, 1H), 2.36-2.64 (m, 2H), 2.86-2.98 (m, 1H), 4.37-4.58 (m, 4H, 2CH2), 5.12-5.19 (dd, J=5.0 and 13.2 Hz, 1H, CH), 6.71 (t, J=5.7 Hz, 1H, NH), 6.89 (t, J=7.3 Hz, 1H, Ar), 7.21 (t, J=7.6 Hz, 2H, Ar), 7.38 (d, J=7.6 Hz, 2H, Ar), 7.48-7.65 (m, 3H, Ar), 8.61 (s, 1H, NH), 11.03 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.57, 31.18, 39.67, 46.20, 51.58, 117.80, 121.20, 121.54, 128.29, 128.62, 130.33, 131.64, 135.59, 139.90, 140.29, 155.22, 168.09, 171.01, 172.84; Anal. calcd. for C21H20N4O4: C, 64.28; H, 5.14; N, 14.28. Found: C, 64.36; H, 4.96; N, 14.17.

Workup

  1. concentrationThe mixture was concentrated
  2. stirringthe residue was stirred with 1N HCl (30 mL)
  3. customThe solid was collected

Sources & evidence

ORD record
ord-9052fb80f9b74c6ca490f46fec4864bc
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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