1-Isocyanato-4-methoxybenzene → HCID 24895848, compound

HRID 240676Notes

Reaction equation

HRID 240676 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].[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]=[C:32]=[O:33])=[CH:27][CH:26]=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:32]([NH:31][C:28]3[CH:27]=[CH:26][C:25]([O:24][CH3:23])=[CH:30][CH:29]=3)=[O:33])[C:9]2=[O:14])[CH2:20][CH2:19][C:18](=[O:21])[NH:17]1

Participants

5

Reactant 3

HCID 794431-Isocyanato-4-methoxybenzeneHCID 81531DiisopropylethylamineHCID 67026973HCID 67026973, compound

Product 1

HCID 24895848HCID 24895848, compoundYield 46.8%

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 4-methoxy-phenyl-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. The mixture was quenched with MeOH and filtered. The resulting solid was rinsed with CH2Cl2 (5 mL) to give 1-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3-(4-methoxy-phenyl)-1-methyl-urea (0.38 g, 46%): mp 245-247° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=1.91 (98%); 1H NMR (DMSO-d6): δ 1.99-2.04 (m, 1H), 2.30-2.37 (m, 1H), 2.56-2.63 (m, 1H), 2.85-2.87 (m, 1H), 2.95 (s, 3H), 3.70 (s, 3H), 4.37 (d, J=17.3 Hz, 1H), 4.44 (d, J=17.4 Hz, 1H), 4.63 (s, 2H), 5.11-5.18 (dd, J=4.9, 13.1 Hz, 1H), 6.84 (d, J=8.9 Hz, 2H), 7.32 (d, J=8.9 Hz, 2H), 7.45 (d, J=7.4 Hz, 1H), 7.53 (t, J=7.4 Hz, 1H), 7.64 (d, J=7.3 Hz, 1H), 8.31 (s, 1H), 11.02 (s, 1H). 13C NMR (DMSO-d6) δ: 22.58, 31.17, 34.64, 46.26, 48.36, 51.57, 55. 10, 113.46, 121.69, 122.01, 128.41, 129.91, 131.91, 133.29, 133.98, 140.13, 154.64, 155.91, 168.02, 171.02, 172.85. Anal Calcd for C23H24N4O5+0.1H2O: C, 63.03; H, 5.57; N, 12.78. Found: C, 62.96; H, 5.48; N, 12.49.

Workup

  1. customThe mixture was quenched with MeOH
  2. filtrationfiltered
  3. washThe resulting solid was rinsed with CH2Cl2 (5 mL)

Sources & evidence

ORD record
ord-3d53b9f52c2247f1bcda56660743c75a
Source dataset
uspto-grants-2014_02
Patent number
US08648096B2

Reaction notes

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