4-Methylbenzoyl Chloride → HCID 58827263, compound

HRID 448458Notes

Reaction equation

HRID 448458 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13].C(N(C(C)C)CC)(C)C.[C:32]1([CH3:41])[CH:37]=[CH:36][C:35]([C:38](Cl)=[O:39])=[CH:34][CH:33]=1>C(Cl)Cl>[O:21]=[C:15]1[CH:14]([N:7]2[C:6](=[O:22])[C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:3][NH:2][C:38](=[O:39])[C:35]3[CH:36]=[CH:37][C:32]([CH3:41])=[CH:33][CH:34]=3)[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

Participants

5

Reactant 3

HCID 134054-Methylbenzoyl ChlorideHCID 81531DiisopropylethylamineHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58827263HCID 58827263, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.16 mmol) in CH2Cl2 (60 ml), was added diisopropylethylamine (0.94 mL, 5.4 mmol) and p-toluoyl chloride (0.43 g, 2.8 mmol). The mixture was then stirred at room temperature overnight and a suspension was obtained. The reaction mixture was quenched with MeOH (1 mL) and washed with H2O (40 mL), 1N HCl (40 mL) and brine (40 mL). The organic layer was dried over MgSO4 and concentrated in vacuo. The resulting mixture was purified by ISCO silica gel flash chromatography (eluent: 3% MeOH in CH2Cl2) to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-methyl-benzamide as a white solid (0.5 g, 61%): mp, 218-220° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=3.3 (97%); 1H NMR (DMSO-d6): δ 2.06-2.11 (m, 1H), 2.36 (s, 3H), 2.54-2.64 (m, 2H), 2.85-2.93 (m, 1H), 4.94 (d, J=5.7 Hz, 2H), 5.15-5.21 (dd, J=5, 12 Hz, 1H), 7.31 (d, J=8.0 Hz, 2H), 9.07 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 20.93, 31.97, 30.92, 38.26, 48.85, 121.81, 127.08, 127.30, 128.87, 131.11, 131.51, 132.98, 134.77, 139.47, 141.35, 166.47, 166.97, 167.54, 169.83, 172.74. Anal Calcd for C22H19N3O5: C, 65.18; H, 4.72; N, 10.36. Found: C, 64.78; H, 4.72; N, 10.07.

Workup

  1. customa suspension was obtained
  2. customThe reaction mixture was quenched with MeOH (1 mL)
  3. washwashed with H2O (40 mL), 1N HCl (40 mL) and brine (40 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe resulting mixture was purified by ISCO silica gel flash chromatography (eluent: 3% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-ea9b230b2eed4e0a9434c9c648f788af
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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