m-Tolyl isocyanate → HCID 59799805, compound

HRID 240673Notes

Reaction equation

HRID 240673 reaction equation
Cl.[CH3:2][NH:3][CH2:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[CH2:7][N:8]([CH:15]1[CH2:20][CH2:19][C:18](=[O:21])[NH:17][C:16]1=[O:22])[C:9]2=[O:14].[C:23]1([CH3:32])[CH:28]=[CH:27][CH:26]=[C:25]([N:29]=[C:30]=[O:31])[CH:24]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[O:22]=[C:16]1[CH:15]([N:8]2[CH2:7][C:6]3[C:10](=[CH:11][CH:12]=[CH:13][C:5]=3[CH2:4][N:3]([CH3:2])[C:30]([NH:29][C:25]3[CH:24]=[C:23]([CH3:32])[CH:28]=[CH:27][CH:26]=3)=[O:31])[C:9]2=[O:14])[CH2:20][CH2:19][C:18](=[O:21])[NH:17]1

Participants

5

Reactant 3

HCID 69303m-Tolyl isocyanateHCID 81531DiisopropylethylamineHCID 67026973HCID 67026973, compound

Product 1

HCID 59799805HCID 59799805, compoundYield 52.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 3-(4-methylaminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.60 g, 1.86 mmol) and m-tolyl isocyanate (0.29 mL, 2.23 mmol) in dry CH2Cl2 (80 ml), was added diisopropylethylamine (0.45 mL g, 2.60 mmol). The mixture was stirred at room temperature overnight and a suspension was obtained. The reaction mixture was filtered, and the solid was rinsed with CH2Cl2 and slurred with acetone to give 1-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-1-methyl-3-m-tolyl-urea as a solid (0.41 g, 52%): mp 208-210° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=2.57 (99%); 1H NMR (DMSO-d6): δ 1.99-2.08 (m, 1H), 2.24 (s, 3H), 2.28-2.35 (m, 1H), 2.55-2.62 (m, 1H), 2.85-2.92 (m, 1H), 2.96 (s, 2H), 4.36 (d, J=17.3 Hz, 1H), 4.43 (d, J=17.3 Hz, 1H), 4.64 (s, 2H), 5.10-5.17 (dd, J=5.1, 13.2 Hz, 1H), 6.78 (d, J=7.4 Hz, 1H), 7.10 (t, J=7.6 Hz, 1H), 7.29-7.25 (m, 2H), 7.45 (d, J=7.2 Hz, 1H), 7.53 (t, J=7.4 Hz, 1H), 7.63 (d, J=7.3 Hz, 1H), 8.38 (s, 1H). 11.02 (s, 1H). 13C NMR (DMSO-d6) δ: 21.17, 22.56, 31.17, 34.71, 46.25, 48.38, 51.56, 117.15, 120.57, 121.71, 122.63, 128.12, 128.43, 129.87, 131.92, 133.87, 137.31, 140.13, 140.27, 155.62, 168.01, 171.01, 172.84. Anal Calcd for C23H24N4O4+0.1 H2O: C, 65.42; H, 5.78; N, 13.27. Found: C, 65.25; H, 5.50; N, 13.14.

Workup

  1. customa suspension was obtained
  2. filtrationThe reaction mixture was filtered
  3. washthe solid was rinsed with CH2Cl2

Sources & evidence

ORD record
ord-54cb8d1cb7d64fde843424daa41e01c3
Source dataset
uspto-grants-2014_02
Patent number
US08648096B2

Reaction notes

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