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Cyclohexanecarboxylic acid → N-{[5-(4-bromophenyl)-5H-imidazo[2,1-a]isoindol-5-yl]methyl}cyclohexanecarboxamide

HRID 46171
Notes
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Reaction equation

HRID 46171 reaction equation
[Cl-].[NH2:2][CH2:3][C:4]1([C:16]2[CH:21]=[CH:20][C:19]([Br:22])=[CH:18][CH:17]=2)[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]2=[NH+:13][CH:14]=[CH:15][N:5]12.C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[CH:42]1([C:48](O)=[O:49])[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1>CN(C=O)C.C(Cl)CCl>[Br:22][C:19]1[CH:20]=[CH:21][C:16]([C:4]2([CH2:3][NH:2][C:48]([CH:42]3[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]3)=[O:49])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]3=[N:13][CH:14]=[CH:15][N:5]23)=[CH:17][CH:18]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 7413Cyclohexanecarboxylic acidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 178509337HCID 178509337, compound

Product 1

HCID 58415567N-{[5-(4-bromophenyl)-5H-imidazo[2,1-a]isoindol-5-yl]methyl}cyclohexanecarboxamide

Reagents, catalysts & solvents 2

HCID 11
1,2-Dichloroethane
Solvent
HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a mixture of 5-(aminomethyl)-5-(4-bromophenyl)-5H-imidazo[2,1-a]isoindol-1-ium chloride (40 mg), EDC (28 mg) and HOAT (13 mg) in DMF (1 mL) was added Hunig's base (75 mg) followed by cyclohexanecarboxylic acid (19 mg). After stirring at 40° C. overnight the mixture was purified by reversed phase HPLC (21×100 mm Phenomenex Gemini, 15-75% MeCN/water containing 0.05% NH4OH over 20 min at 20 mL/min) to give title compound as a white solid. HRMS. Found, 450.1186; calcd for (M+H)+, 450.1176. 1H NMR (500 MHz, CDCl3): δ 7.85 (d, J=7.59 Hz, 1 H); 7.48 (d, J=8.42 Hz, 2 H); 7.46-7.40 (m, 1 H); 7.35-7.28 (m, 3 H); 7.07 (d, J=8.43 Hz, 2 H); 7.03 (d, J=1.34 Hz, 1 H); 4.84 (t, J=6.19 Hz, 1 H); 4.55 (dd, J=13.97, 6.66 Hz, 1 H); 4.24 (dd, J=13.99, 5.93 Hz, 1 H); 1.75-1.49 (m, 5 H); 1.39 (d, J=9.99 Hz, 1 H); 1.28 (d, J=12.70 Hz, 1 H); 1.05 (m, 4 H).

Workup

  1. customwas purified by reversed phase HPLC (21×100 mm Phenomenex Gemini, 15-75% MeCN/water containing 0.05% NH4OH over 20 min at 20 mL/min)

Sources & evidence

ORD record
ord-b52de33b86f14b5dadedf4fd2796f9b0
Source dataset
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08541595B2

Reaction notes

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