Cesium carbonate → 2-{[4-(3-fluoropyridin-2-yl)piperazin-1-yl]methyl}-1H-benzimidazole

HRID 898723

Reaction equation

HRID 898723 reaction equation
[F:1][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][CH:7]=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>[F:1][C:2]1[C:3]([N:8]2[CH2:9][CH2:10][N:11]([CH2:15][C:16]3[NH:20][C:19]4[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=4[N:17]=3)[CH2:12][CH2:13]2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 785712-ChloromethylbenzimidazoleHCID 1349871-(3-Fluoro-2-pyridinyl)piperazine

Product 1

HCID 99664892-{[4-(3-fluoropyridin-2-yl)piperazin-1-yl]methyl}-1H-benzimidazoleYield 36.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The product of Example 28B (0.50 g, 2.76 mmol), 2-chloromethyl-1H-benzimidazole (0.48 g, 2.90 mmol), and cesium carbonate (1.8 g, 5.52 mmol) were combined in N,N-dimethylformamide (28 mL) at 23° C. and stirred for 1.25 hours. The mixture was concentrated under reduced pressure and rinsed with 10% methanol/dichloromethane. The solid was filtered off and the filtrate concentrated under reduced pressure. The residue was impregnated onto flash silica gel and chromatographed on flash silica gel (10% methanol/dichloromethane) to afford 311 mg (36% yield) of the title compound. mp 210-212°° C.; 1H NMR (300 MHz, DMSO-d6) δ 2.62 (m, 4H), 3.43 (m, 4H), 3.78 (s, 2H), 6.87 (m, 1H), 7.14 (m, 2H), 7.50 (m, 3H), 8.00 (m, 1H); MS (APCI) m/e 312 (M+H)+; Anal. calcd for C17H18FN5 0.4 H2O: C, 64.10; H, 5.95; N, 21.98. Found: C, 64.16; H, 5.86; N, 21.95.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. washrinsed with 10% methanol/dichloromethane
  3. filtrationThe solid was filtered off
  4. concentrationthe filtrate concentrated under reduced pressure
  5. customchromatographed on flash silica gel (10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-8537875e22a64c91a5b29651721d11f4
Source dataset
uspto-grants-2008_04
Patent number
US07351828B2

Linked notes

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