Benzoyl chloride, 3,4-dichloro- → HCID 57730505, compound

HRID 331594Notes

Reaction equation

HRID 331594 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])[C:7]2=[O:22].[Cl:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:32]=1[Cl:33])[C:27](Cl)=[O:28].CCN(C(C)C)C(C)C>C1COCC1>[Cl:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:32]=1[Cl:33])[C:27]([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]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:7]2=[O:22])=[O:28]

Participants

5

Reactant 3

HCID 76403Benzoyl chloride, 3,4-dichloro-HCID 81531DiisopropylethylamineHCID 670197065-(Aminomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione hydrochloride

Product 1

HCID 57730505HCID 57730505, compoundYield 89.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred mixture of 5-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.97 g, 3.00 mmol) and 3,4-dichlorobenzoyl chloride (0.69 g, 3.30 mmol) in THF (20 mL), was added DIPEA (1.05 mL, 6.00 mmol) at room temperature under nitrogen. The mixture was heated to 40° C. for 18 h then cooled to rt. The solvent was removed in vacuo and the residue was dissolved in EtOAc (100 mL). The organic layer was washed with dil. aq. HCl (2×150 mL), sat. NaHCO3 (2×150 mL), water (100 mL), dried (MgSO4) and then concentrated. The product was dried in vacuo to give 3,4-dichloro-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-benzamide as a white solid (1.23 g, 89% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 9.40 min (98.44%); mp: 253-255° C.; 1H NMR (DMSO-d6) δ 2.03-2.07 (m, 1H, CHH), 2.43-2.62 (m, 2H, CHH, CHH), 2.81-2.96 (m, 1H, CHH), 4.65 (d, J=5.7 Hz, 2H, CH2), 5.15 (dd, J=5.2, 12.5 Hz, 1H, CH), 7.77-7.92 (m, 5H, Ar), 8.14 (d, J=1.8 Hz, 1H, Ar), 9.40 (t, J=5.7 Hz, 1H, NH), 11.13 (s, 1H, NH); 13C NMR (DMSO-d6) δ 21.99, 30.93, 42.77, 49.01, 122.14, 123.57, 127.62, 129.27, 129.90, 130.81, 131.36, 131.62, 133.55, 134.23, 134.29, 147.07; Anal Calcd for C21H15N3O5Cl2: C, 54.80; H, 3.28; N, 9.13. Found: C, 54.76; H, 3.29; N, 8.87.

Workup

  1. temperaturethen cooled to rt
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in EtOAc (100 mL)
  4. washThe organic layer was washed with dil. aq. HCl (2×150 mL), sat. NaHCO3 (2×150 mL), water (100 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe product was dried in vacuo

Sources & evidence

ORD record
ord-444b59006b0f41e3b782c5e949031d5e
Source dataset
uspto-grants-2014_11
Patent number
US08877780B2

Reaction notes

Loading…