Chlorosuccinimide → HCID 58501775, compound

HRID 625651Notes

Reaction equation

HRID 625651 reaction equation
C1C(=O)N([Cl:8])C(=O)C1.[Br:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[CH:16]=[C:15]([C:20]1[NH:24][C:23]([C@@H:25]3[CH2:29][C@H:28]([CH3:30])[CH2:27][N:26]3[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])=[N:22][CH:21]=1)[CH:14]=[CH:13]2>CN(C=O)C>[Br:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[CH:16]=[C:15]([C:20]1[N:24]=[C:23]([C@@H:25]3[CH2:29][C@H:28]([CH3:30])[CH2:27][N:26]3[C:31]([O:33][C:34]([CH3:36])([CH3:35])[CH3:37])=[O:32])[NH:22][C:21]=1[Cl:8])[CH:14]=[CH:13]2

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 58498713HCID 58498713, compound

Product 1

HCID 58501775HCID 58501775, compoundYield 37.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

NCS (203 mg, 1.52 mmol) was added to a solution of (2S,4S)-tert-butyl 2-(5-(6-bromonaphthalen-2-yl)-1H-imidazol-2-yl)-4-methylpyrrolidine-1-carboxylate (560 mg, 1.39 mmol) in dry DMF (15 mL) and the mixture was heated at 50° C. for 16 h. The solvent was removed by nitrogen purge and the residue was purified with a Thompson 90 g silica gel cartridge (gradient elution 5%-100% B over 2 L; Solvent B=ethyl acetate and Solvent A=hexanes) to yield (2S,4S)-tert-butyl 2-(4-(6-bromonaphthalen-2-yl)-5-chloro-1H-imidazol-2-yl)-4-methylpyrrolidine-1-carboxylate (255 mg) as a tan foam. For purpose of characterization, approximately 20 mg was dissolved in methanol (2 mL) and subject to prep HPLC (gradient 0-100% B over a 25 min at 40 ml/min) on a PHENOMENEX® Luna column (30×100 mm, 10u); Solvent B=95% CH3CN-5% H2O-10 mM NH4OAc and A=5% CH3CN-95% H2O-10 mM NH4OAc. LC-MS retention time 2.61 min; calcd. for C23H26BrClN3O2: 492.09 m/z. found 492.03 [M+H]. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 2.0×50 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 0.8 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 4 min, a hold time of 1 min and an analysis time of 5 min where Solvent A was 5% methanol/95% water/0.1% TFA and Solvent B was 95% methanol/5% water/0.1% TFA. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (500 MHz, MeOD) δ ppm 8.18 (s, 1H), 8.09 (s, 1H), 7.91 (br. s, 2H), 7.83 (d, J=8.6 Hz, 1H), 7.63 (d, J=8.6 Hz, 1H), 4.79-4.75 (m, 1H), 3.78 (t, J=8.9 Hz, 1H), 3.19 (t, J=10.4 Hz, 1H), 2.49 (quin, J=6.1 Hz, 1H), 2.36-2.32 (m, 1H), 1.78 (q, J=11.9 Hz, 1H), 1.45/1.24 (s, 9H), 1.15 (d, J=6.1 Hz, 3H).

Workup

  1. customThe solvent was removed by nitrogen
  2. custompurge
  3. customthe residue was purified with a Thompson 90 g silica gel cartridge (gradient elution 5%-100% B over 2 L; Solvent B=ethyl acetate and Solvent A=hexanes)

Sources & evidence

ORD record
ord-d7efb285afa7474d93c1b2ae3bbfffaf
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

Loading…