Triethylamine → HCID 16117475, compound

HRID 448299Notes

Reaction equation

HRID 448299 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[CH2:13][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].[CH3:29][O:30][CH2:31][C:32](Cl)=[O:33]>C1COCC1>[O:28]=[C:22]1[CH:21]([N:14]2[CH2:13][C:12]3[C:16](=[CH:17][CH:18]=[CH:19][C:11]=3[CH2:10][NH:9][C:32](=[O:33])[CH2:31][O:30][CH3:29])[C:15]2=[O:20])[CH2:26][CH2:25][C:24](=[O:27])[NH:23]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 96623Methoxyacetyl chlorideHCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 16117475HCID 16117475, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (0.5 g, 5.0 mmol) was added to a stirred 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 methoxyacetyl chloride (0.3 g, 2.7 mmol) in THF (30 mL) at room temperature. The mixture was stirred at room temperature overnight. Reaction mixture was quenched with methanol (1 mL) and then concentrated. The residue was stirred with 1N HCl (30 mL) for 30 minutes 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-acetamide (0.4 g, 57%) as a white solid: mp 232-234° C.; 1H NMR (DMSO-d6) δ 2.00-2.04 (m, 1H), 2.32-2.64 (m, 2H), 2.85-3.00 (m, 1H), 3.31 (s, 3H, CH3), 3.87 (s, 2H, CH2), 4.35 (d, J=6.2 Hz, 2H, CH2), 4.41 (d, J=17.3 Hz, 1H), 4.49 (d, J=17.3 Hz, 1H), 5.10-5.17 (dd, J=5.0 and 13.2 Hz, 1H, CH), 7.45-7.64 (m, 3H, Ar), 8.46 (t, J=5.8 Hz, 1H, NH), 11.00 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.57, 31.16, 38.42, 46.18, 51.54, 58.61, 71.46, 121.60, 128.23, 130.69, 131.56, 134.65, 140.01, 168.03, 169.20, 170.97, 172.82, Anal. calcd. for C17H19N3O5: C, 59.12; H, 5.55; N, 12.17. Found: C, 59.10; H, 5.51; N, 12.05.

Workup

  1. customReaction mixture
  2. customwas quenched with methanol (1 mL)
  3. concentrationconcentrated
  4. stirringThe residue was stirred with 1N HCl (30 mL) for 30 minutes
  5. filtrationfiltered

Sources & evidence

ORD record
ord-1b7ef03bc63449f0a692a02198884126
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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