Cesium carbonate → 2-((R)-2-Methyl-4-pyridin-2-yl-piperazin-1-ylmethyl)-1H-benzoimidazole

HRID 898720Notes

Reaction equation

HRID 898720 reaction equation
[CH3:1][C@H:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[CH2:3]1.Cl[CH2:15][C:16]1[NH:20][C:19]2[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=2[N:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH3:1][C@@H:2]1[CH2:3][N:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[CH2:5][CH2:6][N:7]1[CH2:15][C:16]1[NH:20][C:19]2[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=2[N:17]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 785712-ChloromethylbenzimidazoleHCID 1519493(3R)-3-methyl-1-pyridin-2-ylpiperazine

Product 1

HCID 98362092-((R)-2-Methyl-4-pyridin-2-yl-piperazin-1-ylmethyl)-1H-benzoimidazoleYield 39%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

The product of Example 26A (0.79 g, 4.43 mmol) and N,N-dimethylformamide (15 mL) at 0° C. was treated with a solution of the 2-chloromethyl-1H-benzimidazole (0.70 g, 4.21 mmol) in N,N-dimethylformamide (15 mL). After 10 minutes, the mixture was treated with cesium carbonate (1.37 mmol, 4.21 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 (1-3% methanol/dichloromethane gradient) to afford 0.50 g (39% yield) of the title compound as a light yellow solid. mp 151-153° C.; 1H NMR (400 MHz, DMSO-d6) δ 1.18 (d, J=6 Hz, 3H), 2.38 (m, 1H), 2.53 (m, 1H), 2.76 (dd, J=8, 11.2 Hz, 1H), 2.83 (m, 1H), 3.03 (m, 1H), 3.69 (d, J=14 Hz, 1H), 3.94 (m, 1H), 4.00 (m, 1H), 4.07 (d, J=14 Hz, 1H), 6.60 (dd, J=4.8, 6.4 Hz, 1H), 6.80 (d, J=8.4 Hz, 1H), 7.13 (m, 2H), 7.60 (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, 70.10; H, 7.03; N, 22.63.

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 (1-3% methanol/dichloromethane gradient)

Sources & evidence

ORD record
ord-6111daacc2794be5bd16197832e88b22
Source dataset
uspto-grants-2008_04
Patent number
US07351828B2

Reaction notes

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