Diisopropylethylamine → HCID 24895899, compound

HRID 240679Notes

Reaction equation

HRID 240679 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:31]=[C:32]=[O:33])[CH:27]=[C:28]([Cl:30])[CH:29]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[Cl:23][C:24]1[CH:25]=[C:26]([NH:31][C:32](=[O:33])[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]=[C:28]([Cl:30])[CH:29]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 944603,5-Dichlorophenyl isocyanateHCID 67026973HCID 67026973, compound

Product 1

HCID 24895899HCID 24895899, compoundYield 86%

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 3,5-dichlorophenyl-isocyanate (0.42 g, 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-(3,5-dichloro-phenyl)-1-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-1-methyl-urea (0.76 g, 86%): mp 285-287° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=6.97 (99%); 1H NMR (DMSO-d6): δ 2.00-2.05 (m, 1H), 2.33-2.40 (m, 1H), 2.57-2.64 (m, 1H), 2.85-2.94 (m, 1H), 2.98 (s, 3H), 4.37 (d, J=17.3 Hz, 1H), 4.45 (d, J=7.4 Hz, 1H), 4.65 (s, 2H), 5.10-5.18 (dd, J=4.9, 13.1 Hz, 1H), 7.13 (s, 1H), 7.45 (d, J=8.9 Hz, 2H), 7.53 (t, J=7.5 Hz, 1H), 7.63-7.67 (m, 3H), 8.80 (s, 1H), 11.01 (s, 1H). 13C NMR (DMSO-d6) δ: 22.57, 31.19, 34.78, 46.26, 48.37, 51.61, 117.44, 120.77, 121.82, 128.51, 129.81, 131.95, 133.40, 133.65, 140.15, 143.05, 155.03, 167.98, 171.00, 172.83. Anal Calcd for C22H20Cl2N4O4+0.2 CH2Cl2: C, 54.16; H, 4.18; N, 11.38, Cl, 17.28. Found: C, 54.34; H, 3.95; N, 11.29, Cl, 17.13.

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-f08ca6fc753849cd9132ec0f0193ae0d
Source dataset
uspto-grants-2014_02
Patent number
US08648096B2

Reaction notes

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