Chlorosuccinimide → HCID 178451933, compound

HRID 625584Notes

Reaction equation

HRID 625584 reaction equation
C1C(=O)N([Cl:8])C(=O)C1.[Br:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[NH:20][C:19]([CH:21]3[CH2:25][CH2:24][CH2:23][N:22]3[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[N:18][CH:17]=2)=[CH:12][CH:11]=1>CN(C=O)C>[Br:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[NH:20][C:19]([C@@H:21]3[CH2:25][CH2:24][CH2:23][N:22]3[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[N:18][C:17]=2[Cl:8])=[CH:12][CH:11]=1

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 547756232-[5-(4-bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 178451933HCID 178451933, compoundYield 95.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

NCS (0.51 g, 3.82 mmol) was added to a solution of tert-butyl 2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (1.0 g, 2.55 mmol) in DMF (25 mL) and the mixture was heated at 50° C. overnight. The volatiles were removed under vacuum. The residue was purified by flash column chromatography (BIOTAGE®), eluting with a gradient of 0 to 10% EtOAc/DCM to afford the partially pure (S)-tert-butyl 2-(5-(4-bromophenyl)-4-chloro-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (1.04 g) as yellow foam. LC-MS retention time 1.99 min; m/z 427.12 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters Sunfire 5u C18 4.6×30 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where Solvent A was 10% MeOH/90% H2O/0.1% TFA and Solvent B was 10% H2O/90% MeOH/0.1% TFA. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (500 MHz, MeOD) δ ppm 7.63 (s, 4H), 4.74-4.81 (m, 1H), 3.64-3.72 (m, 1H), 3.45-3.55 (m, 1H), 2.27-2.42 (m, 1H), 2.00-2.15 (m, 2H), 1.90-2.00 (m, 1H), 1.48 (m, 3H), 1.27 (m, 6H).

Workup

  1. customThe volatiles were removed under vacuum
  2. customThe residue was purified by flash column chromatography (BIOTAGE®)
  3. washeluting with a gradient of 0 to 10% EtOAc/DCM

Sources & evidence

ORD record
ord-7822dc92706d49189c84169993fff490
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

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