Tetrabutylammonium Fluoride → 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-4-(2-hydroxy-ethoxy)-1H-benzoimidazole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide

HRID 18605Notes

Reaction equation

HRID 18605 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([NH:10][C:11]([C:13]2[N:17]([CH2:18][C:19](=[O:28])[NH:20][C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][N:22]=3)[C:16]3[CH:29]=[CH:30][CH:31]=[C:32]([O:33][CH2:34][CH2:35][O:36][Si](C(C)(C)C)(C)C)[C:15]=3[N:14]=2)=[O:12])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.C(O)(=O)C>[CH:1]([N:4]1[CH2:5][CH2:6][CH:7]([NH:10][C:11]([C:13]2[N:17]([CH2:18][C:19](=[O:28])[NH:20][C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][N:22]=3)[C:16]3[CH:29]=[CH:30][CH:31]=[C:32]([O:33][CH2:34][CH2:35][OH:36])[C:15]=3[N:14]=2)=[O:12])[CH2:8][CH2:9]1)([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 865958834-[2-(tert-Butyl-dimethyl-silanyloxy)-ethoxy]-1-[(5-chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-benzoimidazole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide

Product 1

HCID 670132371-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-4-(2-hydroxy-ethoxy)-1H-benzoimidazole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

250 mg (0.40 mmol) 4-[2-(tert-Butyl-dimethyl-silanyloxy)-ethoxy]-1-[(5-chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-benzoimidazole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide were dissolved in 15 mL THF. 435 μl of a 1 M TBAF-solution in THF and 26 μl acetic acid were added. The resulting mixture was stirred for 48 h at room temperature. The reaction mixture was concentrated under reduced pressure. The residue was taken up in 50 mL CH2Cl2 and washed once with a saturated NaHCO3-solution and five times with water. The organic layer was dried over anhydrous MgSO4 and concentrated under vacuo. Final purification by preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid) gave pure 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-4-(2-hydroxy-ethoxy)-1H-benzoimidazole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide as its formiate in form of a colorless amorphous material. The title compound was transformed into its acetate. Yield: 132 mg MS (ES+): m/e=515, chloro pattern.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. washwashed once with a saturated NaHCO3-solution and five times with water
  3. dry with materialThe organic layer was dried over anhydrous MgSO4
  4. concentrationconcentrated under vacuo
  5. customFinal purification by preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid)

Sources & evidence

ORD record
ord-899474a12ad541a081698f83ddb4101c
Source dataset
uspto-grants-2010_06
Patent number
US07741341B2

Reaction notes

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