Cesium carbonate → 2-[(2-methyl-4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole

HRID 898716Notes

Reaction equation

HRID 898716 reaction equation
Br.[CH3:2][CH:3]1[NH:8][CH2:7][CH2:6][N:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[CH2:4]1.Cl[CH2:16][C:17]1[NH:21][C:20]2[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=2[N:18]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH3:2][CH:3]1[CH2:4][N:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[CH2:6][CH2:7][N:8]1[CH2:16][C:17]1[NH:21][C:20]2[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=2[N:18]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 785712-ChloromethylbenzimidazoleHCID 118491863-Methyl-1-pyridin-2-ylpiperazine hydrobromide

Product 1

HCID 99444162-[(2-methyl-4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazoleYield 36%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

The product from Example 24A (0.50 g, 1.93 mmol) in N,N-dimethylformamide (10 mL) at 0° C. was slowly treated with a solution of 2-chloromethyl-1H-benzimidazole (0.31 g, 1.83 mmol) in N,N-dimethylformamide (10 mL). After 5 minutes, the mixture was treated with cesium carbonate (0.60 mmol, 1.83 mmol) and the cooling bath was removed. After 1 hour, the reaction mixture was diluted with ethyl acetate and washed with water (3×) and brine, dried over Na2SO4, filtered, and the filtrate concentrated under reduced pressure. The residue was chromatographed on flash silica gel (2% methanol/dichloromethane) to afford 201 mg (36% yield) of the title compound. mp 207-209° C.; 1H NMR (300 MHz, DMSO-d6) δ 1.18 (d, J=6.0 Hz, 3H), 2.38 (m, 1H), 2.52 (m, 1H), 2.78 (m, 2H), 3.02 (m, 1H), 3.67 (d, J=14.4 Hz, 1H), 3.97 (m, 2H), 4.08 (d, J=14.4 Hz, 1H), 6.62 (dd, J=5.1, 6.9 Hz, 1H), 6.81 (d, J=8.4 Hz, 1H), 7.14 (m, 2H), 7.50 (m, 3H), 8.08 (m, 1H), 12.22 (bs, 1H); MS (ESI) m/e 308 (M+H)+; Anal. calcd for C18H21N5: C, 70.33; H, 6.89; N, 22.78. Found: C, 70.15; H, 6.92; N, 22.46.

Workup

  1. customthe cooling bath was removed
  2. waitAfter 1 hour
  3. additionthe reaction mixture was diluted with ethyl acetate
  4. washwashed with water (3×) and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under reduced pressure
  8. customThe residue was chromatographed on flash silica gel (2% methanol/dichloromethane)

Sources & evidence

ORD record
ord-e5df408bc9de4d1292f77e934d0c7ac2
Source dataset
uspto-grants-2008_04
Patent number
US07351828B2

Reaction notes

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