Benzene, 1-chloro-3-isocyanato- → HCID 24895847, compound

HRID 240675Notes

Reaction equation

HRID 240675 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].[Cl:23][C:24]1[CH:25]=[C:26]([N:30]=[C:31]=[O:32])[CH:27]=[CH:28][CH:29]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[Cl:23][C:24]1[CH:25]=[C:26]([NH:30][C:31](=[O:32])[N:3]([CH2:4][C:5]2[CH:13]=[CH:12][CH:11]=[C:10]3[C:6]=2[CH2:7][N:8]([CH:15]2[CH2:20][CH2:19][C:18](=[O:21])[NH:17][C:16]2=[O:22])[C:9]3=[O:14])[CH3:2])[CH:27]=[CH:28][CH:29]=1

Participants

5

Reactant 3

HCID 17968Benzene, 1-chloro-3-isocyanato-HCID 81531DiisopropylethylamineHCID 67026973HCID 67026973, compound

Product 1

HCID 24895847HCID 24895847, compoundYield 82.9%

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 3-chloro-phenyl-isocyanate (0.27 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 3-(3-chloro-phenyl)-1-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-1-methyl-urea (0.68 g, 82%): mp 193-195° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=3.29 (99%); 1H NMR (DMSO-d6): δ 2.00-2.04 (m, 1H), 2.32-2.38 (m, 1H), 2.56-2.63 (m, 1H), 2.85-2.92 (m, 1H), 2.98 (s, 3H), 4.38 (d, J=17.3 Hz, 1H), 4.45 (d, J=17.3 Hz, 1H), 4.65 (s, 2H), 5.10-5.18 (dd, J=4.5, 13.2 Hz, 1H), 7.00 (d, J=7.8 Hz, 1H), 7.26 (t, J=8.0 Hz, 1H), 7.46-7.41 (In, 2H), 7.53 (t, J=7.5 Hz, 1H), 7.64-7.67 (m, 2H), 8.65 (s, 1H), 11.13 (s, 1H). 13C NMR (DMSO-d6) δ: 22.57, 31.19, 34.76, 46.27, 48.37, 51.60, 118.00, 119.08, 121.42, 121.77, 128.48, 129.85, 129.92, 131.93, 132.69, 133.62, 140.15, 142.04, 155.34, 168.00, 171.01, 172.84. Anal Calcd for C22H21ClN4O4: C, 59.93; H, 4.80; N, 12.71, Cl, 8.04. Found: C, 59.30; H, 4.66; N, 12.33, Cl, 8.36.

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-c9443a48caec4f6ca61644f9ef3101f4
Source dataset
uspto-grants-2014_02
Patent number
US08648096B2

Reaction notes

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