Triethylamine → 3,4-dichloro-N-[2-(3-methyl-2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-benzamide

HRID 63419

Reaction equation

HRID 63419 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[N:8]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[CH2:7]2.[Cl:22][C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][C:31]=1[Cl:32])[C:26](Cl)=[O:27].[CH2:33](N(CC)CC)C>CN(C)C=O.O>[Cl:22][C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][C:31]=1[Cl:32])[C:26]([NH:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[N:8]([C:14]1([CH3:33])[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[CH2:7]2)=[O:27]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 76403Benzoyl chloride, 3,4-dichloro-HCID 665895253-(5-(aminomethyl)-1-oxo-2,3-dihydro-1H-isoindol-2-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 690489933,4-dichloro-N-[2-(3-methyl-2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-benzamideYield 79.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.4 g, 1.20 mmol) and 3,4-dichlorobenzoyl chloride (0.26 g, 1.20 mmol) in N,N-dimethylformamide (15 mL), was added triethylamine (0.34 mL, 2.40 mmol) at room temperature under nitrogen. After 2 h, the mixture was diluted with water (40 mL) and stirred for 1 h. The product was isolated by filtration, washed with water (50 mL) and dried in vacuo providing 3,4-dichloro-N-[2-(3-methyl-2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-benzamide as an off-white solid (0.44 g, 79% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 45/55 CH3CN/0.1% H3PO4, 3.46 min (96.23%); mp: 220-222° C.; 1H NMR (DMSO-d6) δ 1.66 (s, 3H), 1.80-1.98 (m, 1H), 2.52-2.82 (m, 3H), 4.51-4.72 (m, 4H), 7.45 (d, J=7.7 Hz, 1H), 7.54 (s, 1H), 7.61 (d, J=7.7 Hz, 1H), 7.78 (d, J=8.3 Hz, 1H), 7.88 (d, J=7.7 Hz, 1H), 8.14 (s, 1H), 9.34 (t, J=5.2 Hz, 1H), 10.86 (br. s., 1H); 13C NMR (DMSO-d6) δ 20.74, 27.81, 29.01, 42.89, 47.65, 57.12, 121.92, 122.59, 127.13, 127.61, 129.24, 130.76, 131.08, 131.31, 134.15, 134.49, 142.41, 143.28, 164.04, 166.97, 172.43, 173.53; LCMS: MH=460 462; Anal Calcd for C22H19Cl2N3O4+1.15H2O: C, 54.93; H, 4.46; N, 8.74. Found: C, 54.60; H, 4.07; N, 8.70.

Workup

  1. customThe product was isolated by filtration
  2. washwashed with water (50 mL)
  3. customdried in vacuo

Sources & evidence

ORD record
ord-5ee23cd8164042cca1efcb2fe7b835cd
Source dataset
uspto-grants-2016_09
Patent number
US09447070B2

Linked notes

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