p-Anisoyl chloride → HCID 58307251, compound

HRID 448436Notes

Reaction equation

HRID 448436 reaction equation
C(N(CC)CC)C.Cl.[NH2:9][CH2:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:12]=1[C:13](=[O:29])[N:14]([CH:21]1[CH2:26][CH2:25][C:24](=[O:27])[NH:23][C:22]1=[O:28])[C:15]2=[O:20].[C:30](Cl)(=[O:39])[C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=1>C1COCC1>[O:28]=[C:22]1[CH:21]([N:14]2[C:13](=[O:29])[C:12]3[C:16](=[CH:17][CH:18]=[CH:19][C:11]=3[CH2:10][NH:9][C:30](=[O:39])[C:31]3[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=3)[C:15]2=[O:20])[CH2:26][CH2:25][C:24](=[O:27])[NH:23]1

Participants

5

Reactant 3

HCID 7477p-Anisoyl chlorideHCID 8471TriethylamineHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58307251HCID 58307251, compoundYield 71.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (0.5 g, 5.0 mmol) was added slowly to a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.0 mmol) and p-anisoyl chloride (0.5 g, 2.8 mmol) in THF (30 mL) at 5-10° C. After 10 minutes, the mixture was stirred at room temperature overnight. The reaction was quenched with methanol (1 mL), and the mixture was concentrated. The residue was stirred with 1N HCl (30 mL) for 1 hour then filtered. The solid was slurried with hot ethanol (15 mL) to give N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-methoxy-benzamide (0.6 g, 71%) as a white solid: mp 193-195° C.; 1H NMR (DMSO-d6) δ 2.06-2.10 (m, 1H), 2.50-2.65 (m, 2H), 2.84-2.97 (m, 1H), 3.83 (s, 3H, OCH3), 4.93 (d, J=5.7 Hz, 2H, CH2), 5.14-5.21 (dd, J=5.4 and 12.7 Hz, 1H, CH), 7.04 (d, J=8.8 Hz, 2H, Ar), 7.69-7.86 (m, 3H, Ar), 7.89 (d, J=8.7 Hz, 2H, Ar), 9.01 (t, J=5.7 Hz, 1H, NH), 11.15 (s, 1H, NH); 13C NMR (DMSO-d6) δ 21.99, 30.94, 38.25, 48.87, 55.36, 113.57, 121.80, 126.10, 127.06, 129.15, 131.51, 133.00, 134.77, 139.63, 161.75, 166.08, 166.99, 167.56, 169.85, 172.77; Anal. calcd. for C22H19N3O6+0.34H2O: C, 61.81; H, 4.64; N, 9.83. Found: C, 61.77; H, 4.54; N, 9.63.

Workup

  1. customThe reaction was quenched with methanol (1 mL)
  2. concentrationthe mixture was concentrated
  3. stirringThe residue was stirred with 1N HCl (30 mL) for 1 hour
  4. filtrationthen filtered

Sources & evidence

ORD record
ord-e09a3dd171304a9797d13aff7192a18f
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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