Triethylamine → HCID 16117209, compound

HRID 448287Notes

Reaction equation

HRID 448287 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][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:22](Cl)(=[O:31])[C:23]1[C:24]([O:29][CH3:30])=[CH:25][CH:26]=[CH:27][CH:28]=1.C(N(CC)CC)C>C1COCC1>[O:21]=[C:15]1[CH:14]([N:7]2[CH2:6][C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:3][NH:2][C:22](=[O:31])[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[O:29][CH3:30])[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 889692-Methoxybenzoyl chlorideHCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 16117209HCID 16117209, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

A suspension of 3-(4-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.7 g, 2.1 mmol) and o-anisoyl chloride (0.4 g, 2.5 mmol) in THF (30 mL) was cooled to 5° C. Triethylamine (0.5 g, 4.8 mmol) was added, and 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) and filtered. The solid was slurried with ethanol (15 mL) to give N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-2-methoxy-benzamide (0.8 g, 94%) as a white solid: mp 236-238° C.; 1H NMR (DMSO-d6) δ 2.01-2.06 (m, 1H), 2.32-2.66 (m, 2H), 2.86-3.01 (m, 1H), 3.88 (s, 3H, OCH3), 4.39-4.61 (m, 4H, 2CH2), 5.12-5.19 (dd, J=4.9 and 13.1 Hz, 1H, CH), 7.02 (t, J=7.4 Hz, 1H, Ar), 7.16 (d, J=8.3 Hz, 1H, Ar), 7.44-7.72 (m, 5H, Ar), 8.77 (t, J=5.6 Hz, 1H, NH), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.60, 31.17, 46.20, 51.55, 55.82, 111.93, 120.41, 121.51, 123.10, 128.24, 130.22, 130.43, 131.57, 132.17, 134.89, 139.94, 156.87, 165.34, 168.09, 171.00, 172.83; Anal. calcd. for C22H21N3O5: C, 64.86; H, 5.20; N, 10.31. Found: C, 64.59; H, 5.01; N, 10.17.

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)
  4. filtrationfiltered

Sources & evidence

ORD record
ord-22489b033f2045f68aa10bc6a163219b
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

Loading…