Diethylamine → 2-(1-(2-hydroxyethyl)-2,6-dioxopiperidin-3-yl)isoindolin-1,3-dione (S)-2-(2-diethylaminoacetamido)-3-methylbutanoate

HRID 1525810Notes

Reaction equation

HRID 1525810 reaction equation
Br[CH2:2][C:3]([NH:5][C@@H:6]([CH:10]([CH3:12])[CH3:11])[C:7]([OH:9])=[O:8])=[O:4].[OH:13][CH2:14][CH2:15][N:16]1[C:21](=[O:22])[CH2:20][CH2:19][CH:18]([N:23]2[C:31](=[O:32])[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:24]2=[O:33])[C:17]1=[O:34].C(NCC)C>C(Cl)Cl>[CH2:15]([N:16]([CH2:17][CH3:18])[CH2:2][C:3]([NH:5][C@@H:6]([CH:10]([CH3:12])[CH3:11])[C:7]([OH:9])=[O:8])=[O:4])[CH3:14].[OH:13][CH2:14][CH2:15][N:16]1[C:21](=[O:22])[CH2:20][CH2:19][CH:18]([N:23]2[C:24](=[O:33])[C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:31]2=[O:32])[C:17]1=[O:34]

Participants

4

Reactant 2

HCID 8021DiethylamineHCID 866187512-(1-(2-hydroxyethyl)-2,6-dioxopiperidin-3-yl)isoindolin-1,3-dione (S)-2-(2-bromoacetamido)-3-methylbutanoate

Product 1

HCID 710827862-(1-(2-hydroxyethyl)-2,6-dioxopiperidin-3-yl)isoindolin-1,3-dione (S)-2-(2-diethylaminoacetamido)-3-methylbutanoateYield 170.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(1-(2-hydroxyethyl)-2,6-dioxopiperidin-3-yl)isoindolin-1,3-dione (S)-2-(2-bromoacetamido)-3-methylbutanoate (120 mg) was dissolved in DCM (8 mL). The mixture was stirred and and diethylamine solution was added slowly dropwise (0.04 mL). The reaction mixture was stirred additionally for 2 hrs at room temperature. The solvent and the residual diethylamine were removed by rotary evaporation in vacuo. 101 mg of white solid were obtained after purification of the crude product by silica gel column chromatography (eluted with acetic ether: petroleum ether=3:1). 1H NMR (CDCl3, ppm) δ 7.94 (d, 1H, J=8.4 Hz), 7.87-7.91 (m, 2H), 7.76-7.79 (m, 2H), 4.97-5.08 (m, 1H), 4.38-4.43 (m, 1H), 4.05-4.30 (m, 3H), 3.25 (dd, 1H, J=4.8, 13.2Hz), 3.05 (s, 2H), 2.95-3.05 (m, 1H), 2.80-2.95 (m, 2H), 2.45-2.58 (m, 4H), 2.10-2.20 (m, 1H), 1.90-2.10 (m, 2H), 1.00-1.20 (m, 7H), 0.95-0.98 (m, 3H), 0.87-0.91 (m, 3H).

Workup

  1. stirringThe reaction mixture was stirred additionally for 2 hrs at room temperature
  2. customThe solvent and the residual diethylamine were removed by rotary evaporation in vacuo

Sources & evidence

ORD record
ord-22c9b33439be4fc68f0f3caeeae212f1
Source dataset
uspto-grants-2015_07
Patent number
US09085563B2

Reaction notes

Loading…