Benzoyl Peroxide → 2-Chloro-6-(4-{[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl]-5-phenylnicotinonitrile

HRID 1354810Notes

Reaction equation

HRID 1354810 reaction equation
[Cl:1][C:2]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)[C:7]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:6][C:3]=1[C:4]#[N:5].C1C(=O)N(Br)C(=O)C1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.[O:49]=[C:50]1[N:54]([CH:55]2[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]2)[C:53]2[CH:61]=[CH:62][CH:63]=[CH:64][C:52]=2[NH:51]1.C(N(C(C)C)CC)(C)C>C(Cl)(Cl)Cl>[Cl:1][C:2]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:58]3[CH2:57][CH2:56][CH:55]([N:54]4[C:53]5[CH:61]=[CH:62][CH:63]=[CH:64][C:52]=5[NH:51][C:50]4=[O:49])[CH2:60][CH2:59]3)=[CH:12][CH:11]=2)[C:7]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:6][C:3]=1[C:4]#[N:5]

Participants

7

Reactant 5

HCID 7187Benzoyl PeroxideHCID 67184N-bromobutanimideHCID 81531DiisopropylethylamineHCID 886381,3-Dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-oneHCID 211031982-Chloro-6-(4-methylphenyl)-5-phenylnicotinonitrile

Product 1

HCID 114098042-Chloro-6-(4-{[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl]-5-phenylnicotinonitrile

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A mixture of 2-chloro-6-(4-methylphenyl)-5-phenylnicotinonitrile (11-4) (1.78 g, 5.84 mmol), NBS (1.14 g, 6.42 mmol) and benzoylperoxide (0.28 g, 1.17 mmol) in chloroform (25 mL) was heated to reflux for 24 h. Concentrated in vacuo and the residue was dissolved in MeOH (15 mL) and THF (15 mL). To this solution was added 4-(2-keto-1-benzimidazolinyl)-piperidine (1.39 g, 6.42 mmol) and diisopropylethylamine (3.8 g, 29.2 mmol). The mixture was stirred overnight and concentrated. The residue was treated with Na2CO3 (20 mL, 2M) and extracted with CH2Cl2. The combined organic layers was dried, filtered and concentrated in vacuo. The solid was purified by silicon gel chromatography (2–4% MeOH in CH2Cl2) to give 2-chloro-6-(4-{[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-5-phenylnicotinonitrile (11-5). 1H NMR (CDCl3) δ 8.70 (s, 1H), 7.98 (s, 1H), 7.37–7.25 (m, 7H), 7.17–7.19 (m, 2H), 7.03–7.09 (m, 4H), 4.31–4.37 (m, 1H), 3.54 (s, 2H), 2.98 (m, 2H), 2.41–2.46 (m, 2H), 2.13–2.18 (m, 2H), 1.78–1.80 (m, 2H). LRMS m/z (M+H) Calcd: 520.0, found: 520.2.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 24 h
  3. concentrationConcentrated in vacuo
  4. dissolutionthe residue was dissolved in MeOH (15 mL)
  5. concentrationconcentrated
  6. additionThe residue was treated with Na2CO3 (20 mL, 2M)
  7. extractionextracted with CH2Cl2
  8. customThe combined organic layers was dried
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe solid was purified by silicon gel chromatography (2–4% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-e54f640c329940b29a501b280246a1d5
Source dataset
uspto-grants-2007_05
Patent number
US07223738B2

Reaction notes

Loading…