Pyrrolidine → 5-(4-bromophenyl)-5-(2-oxo-2-pyrrolidin-1-ylethyl)-5H-imidazo[2,1-a]isoindole

HRID 46168Notes

Reaction equation

HRID 46168 reaction equation
[CH:1]1[CH:6]=[N:5][C:4]2N(O)N=N[C:3]=2C=1.FC(F)(F)C([O-])=O.[Br:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2([CH2:37][C:38]([OH:40])=O)[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]3=[NH+:34][CH:35]=[CH:36][N:26]23)=[CH:21][CH:20]=1.CCN(C(C)C)C(C)C.N1CCCC1>CN(C=O)C.C(Cl)CCl>[Br:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]2([CH2:37][C:38](=[O:40])[N:5]3[CH2:4][CH2:3][CH2:1][CH2:6]3)[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]3=[N:34][CH:35]=[CH:36][N:26]23)=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 1785249895-(4-bromophenyl)-5-(carboxymethyl)-5H-imidazo[2,1-a]isoindol-1-ium trifluoroacetate

Product 1

HCID 462023775-(4-bromophenyl)-5-(2-oxo-2-pyrrolidin-1-ylethyl)-5H-imidazo[2,1-a]isoindole

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of EDC (49.2 mg) and HOAT (17.5 mg) was added a solution of 5-(4-bromophenyl)-5-(carboxymethyl)-5H-imidazo[2,1-a]isoindol-1-ium trifluoroacetate (62 mg) and Hunig's base (0.134 mL) in DMF (1 mL) followed by pyrrolidine (22.8 mg). The reaction mixture was stirred overnight at room temperature and was then purified by reversed phase HPLC (21×100 mm Phenomenex Gemini, 15-70% MeCN/water containing 0.05% NH4OH over 20 min at 20 mL/min) to give title compound as a white solid. HRMS. Found, 422.0873; calcd for (M+H)+, 422.0863. 1H NMR (500 MHz, CDCl3): δ 7.84 (d, J=7.60 Hz, 1 H); 7.47 (d, J=1.30 Hz, 1 H); 7.42-7.39 (m, 3 H); 7.29-7.26 (m, 3 H); 6.91 (dd, J=21.03, 8.48 Hz, 2 H); 3.71 (d, J=16.82 Hz, 1 H); 3.42 (t, J=6.89 Hz, 2 H); 3.34 (dt, J=9.85, 6.85 Hz, 1 H); 3.18 (dt, J=9.89, 6.80 Hz, 1 H); 2.86 (d, J=16.81 Hz, 1 H); 1.95-1.79 (m, 4 H).

Workup

  1. customwas then purified by reversed phase HPLC (21×100 mm Phenomenex Gemini, 15-70% MeCN/water containing 0.05% NH4OH over 20 min at 20 mL/min)

Sources & evidence

ORD record
ord-6d64d62dbb1341fd91bfb24ba02aa77c
Source dataset
uspto-grants-2013_09
Patent number
US08541595B2

Reaction notes

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