2-Chlorobenzoyl chloride → HCID 58827321, compound

HRID 448462Notes

Reaction equation

HRID 448462 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.[Cl:32][C:33]1[CH:41]=[CH:40][CH:39]=[CH:38][C:34]=1[C:35](Cl)=[O:36]>C(Cl)Cl>[Cl:32][C:33]1[CH:41]=[CH:40][CH:39]=[CH:38][C:34]=1[C:35]([NH: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])=[O:36]

Participants

5

Reactant 3

HCID 691102-Chlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58827321HCID 58827321, compoundYield 60%

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 2-chlorobenzoyl chloride (0.5 g, 2.8 mmol). The mixture was stirred at room temperature overnight. The reaction mixture was quenched with MeOH (1 mL) and then washed with H2O (40 mL), 1N HCl (40 mL), brine (40 mL), and dried over MgSO4. The organic layer was concentrated in vacuo, and the resulting oil was purified by ISCO silica gel flash chromatography (eluent: 3% MeOH in CH2Cl2 for 10 min, then 5% MeOH in CH2Cl2 for 10 min):) to afford 2-chloro-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-benzamide as a white solid (0.55 g, 60%): mp, 209-211° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=3.0 min (99%); 1H NMR (DMSO-d6): δ 2.06-2.11 (m, 1H), 2.53-2.64 (m, 2H), 2.87-2.93 (m, 1H), 4.92 (d, J=5.9 Hz, 2H), 5.14-5.20 (dd, J=5, 12 Hz, 1H), 7.39-7.57 (m, 4H), 7.82-7.89 (m, 3H), 9.12 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 21.96, 30.91, 38.10, 48.86, 121.95, 127.15, 128.97, 129.62, 129.83, 130.94, 131.54, 133.10, 134.80, 136.49, 138.74, 166.77, 166.93, 167.48, 169.80, 172.74. Anal Calcd for C21H16ClN3O5: C, 59.23; H, 3.79; N, 9.87; Cl, 8.33. Found: C, 59.24; H, 3.45; N, 9.71; Cl, 8.32.

Workup

  1. customThe reaction mixture was quenched with MeOH (1 mL)
  2. washwashed with H2O (40 mL), 1N HCl (40 mL), brine (40 mL)
  3. dry with materialdried over MgSO4
  4. concentrationThe organic layer was concentrated in vacuo
  5. customthe resulting oil was purified by ISCO silica gel flash chromatography (eluent
  6. wait3% MeOH in CH2Cl2 for 10 min

Sources & evidence

ORD record
ord-23ced193c7624a4d9ab781c8ab77f8bc
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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