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

HRID 1869274Notes

Reaction equation

HRID 1869274 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:15][C:12]([C:13]#[N:14])=[C:11]([Cl:23])[N:10]=2)=[CH:5][CH:4]=1.[O:24]=[C:25]1[N:29]([CH:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[C:28]2[CH:36]=[CH:37][CH:38]=[CH:39][C:27]=2[NH:26]1>CO.C1COCC1>[Cl:23][C:11]1[N:10]=[C:9]([C:6]2[CH:7]=[CH:8][C:3]([CH2:2][N:33]3[CH2:32][CH2:31][CH:30]([N:29]4[C:28]5[CH:36]=[CH:37][CH:38]=[CH:39][C:27]=5[NH:26][C:25]4=[O:24])[CH2:35][CH2:34]3)=[CH:4][CH:5]=2)[C:16]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:15][C:12]=1[C:13]#[N:14]

Participants

5

Reactant 2

HCID 886381,3-Dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-oneHCID 866076536-[4-(Bromomethyl)phenyl]-2-chloro-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 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To the solution of 6-[4-(bromomethyl)phenyl]-2-chloro-5-phenylnicotinonitrile (1-5; 0.078 g, 0.203 mmol) in MeOH (1 mL) and THF (1 mL) was added 4-(2-keto-1-benzimidazolinyl)-piperidine (0.066 g, 0.305 mmol) and DIEPA (0.131 g, 1.02 mmol). The mixture was stirred at rt overnight and concentrated. The residue was treated with aqueous Na2CO3 solution (5 mL, 2 M) and extracted with CH2Cl2 (3×10 mL). The combined organic layer was dried, filtered and concentrated. The residue was purified by silica gel chromatography (3-5% 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 (1-6). 1H-NMR (500 MHz, CDCl3) δ 7.98 (s, 1H), 7.31-7.37 (m, 4H), 7.25-7.29 (m, 4H), 7.17-7.19 (m, 2H), 7.05-7.09 (m, 3H), 4.31-4.36 (m, 1H), 3.54 (s, 2H), 2.97-2.99 (m, 2H), 2.41-2.47 (m, 2H), 2.12-2.17 (m, 2H), 1.78-1.80 (m, 2H). LRMS m/z (M+H) Calcd: 520.0, found: 520.0.

Workup

  1. concentrationconcentrated
  2. additionThe residue was treated with aqueous Na2CO3 solution (5 mL, 2 M)
  3. extractionextracted with CH2Cl2 (3×10 mL)
  4. customThe combined organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (3-5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-8cbc334bf05b4a269a3221a49568b13f
Source dataset
uspto-grants-2009_12
Patent number
US07638530B2

Reaction notes

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