4-Methylbenzoyl Chloride → HCID 57730522, compound

HRID 63464Notes

Reaction equation

HRID 63464 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].[CH3:23][C:24]1[CH:32]=[CH:31][C:27]([C:28](Cl)=[O:29])=[CH:26][CH:25]=1.CCN(C(C)C)C(C)C>CC#N>[O:21]=[C:15]1[CH:14]([N:8]2[C:7](=[O:22])[C:6]3[C:10](=[CH:11][CH:12]=[C:4]([CH2:3][NH:2][C:28](=[O:29])[C:27]4[CH:31]=[CH:32][C:24]([CH3:23])=[CH:25][CH:26]=4)[CH:5]=3)[C:9]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

Participants

5

Reactant 3

HCID 134054-Methylbenzoyl ChlorideHCID 81531DiisopropylethylamineHCID 670197065-(Aminomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione hydrochloride

Product 1

HCID 57730522HCID 57730522, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

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 4-methyl-benzoyl chloride (0.46 g, 3.00 mmol) in MeCN (20 mL), was added DIPEA (1.05 mL, 6.00 mmol) at room temperature under nitrogen. After 1 h, 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), water (100 mL), dried (MgSO4) and then concentrated. The product was triturated in Et2O (50 mL) for 18 h then filtered and dried in vacuo to give N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-4-methyl-benzamide as a white solid (0.85 g, 70% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 4.48 min (96.54%); mp: 194-196° C.; 1H NMR (DMSO-d6) δ 1.97-2.14 (m, 1H, CHH), 2.36 (s, 3H, CH3), 2.44-2.71 (m, 2H, M01), 2.78-3.04 (m, 1H, CHH), 4.63 (d, J=5.9 Hz, 2H, CH2), 5.14 (dd, J=5.4, 12.9 Hz, 1H, CH), 7.30 (d, J=7.9 Hz, 2H, Ar), 7.75-7.86 (m, 4H, Ar), 7.90 (d, J=7.6 Hz, 1H, Ar), 9.14 (t, J=5.9 Hz, 1H, NH), 11.12 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.96, 21.99, 30.93, 42.57, 49.01, 121.95, 123.53, 127.27, 128.91, 129.77, 131.14, 131.60, 133.42, 141.37, 147.73, 166.30, 166.99, 167.13, 169.80, 172.72; LCMS: MH=406; Anal Calcd for C22H19N3O5+0.1H2O: C, 64.89; H, 4.75; N, 10.32. Found: C, 64.72; H, 4.70; N, 10.15.

Workup

  1. customthe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in EtOAc (100 mL)
  3. washThe organic layer was washed with dil. aq. HCl (2×150 mL), water (100 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe product was triturated in Et2O (50 mL) for 18 h
  7. filtrationthen filtered
  8. customdried in vacuo

Sources & evidence

ORD record
ord-b02a9c04f2594478a2baa35483530b06
Source dataset
uspto-grants-2016_09
Patent number
US09447070B2

Reaction notes

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