Ethylene Glycol → 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid 2-hydroxy-ethyl ester

HRID 18548Notes

Reaction equation

HRID 18548 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]2[O:11][N:10]=[C:9]([CH2:12][N:13]3[C:17]4[CH:18]=[CH:19][CH:20]=[C:21]([C:22]([OH:24])=[O:23])[C:16]=4[N:15]=[C:14]3[C:25](=[O:36])[NH:26][CH:27]3[CH2:32][CH2:31][N:30]([CH:33]([CH3:35])[CH3:34])[CH2:29][CH2:28]3)[CH:8]=2)=[CH:4][CH:3]=1.C1CCC(N=C=NC2CCCCC2)CC1.[CH2:52](O)[CH2:53][OH:54]>CN(C=O)C.CN(C1C=CN=CC=1)C>[OH:54][CH2:53][CH2:52][O:23][C:22]([C:21]1[C:16]2[N:15]=[C:14]([C:25](=[O:36])[NH:26][CH:27]3[CH2:32][CH2:31][N:30]([CH:33]([CH3:34])[CH3:35])[CH2:29][CH2:28]3)[N:13]([CH2:12][C:9]3[CH:8]=[C:7]([C:5]4[S:6][C:2]([Cl:1])=[CH:3][CH:4]=4)[O:11][N:10]=3)[C:17]=2[CH:18]=[CH:19][CH:20]=1)=[O:24]

Participants

6

Reactant 3

HCID 174Ethylene GlycolHCID 10868DicyclohexylcarbodiimideHCID 112378401-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid

Product 1

HCID 670127761-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid 2-hydroxy-ethyl ester

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

50 mg (0.08 mmol) 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid were dissolved in 4 mL DMF. Subsequently 20 mg DMAP, 34.3 mg (0.16 mmol) DCC and 46 μl (0.83 mmol) ethylene glycol were added. The resulting mixture was stirred for 8 h at 60° C. and then concentrated under removed pressure. The remaining residue was purified by preparative HPLC (CH3CN/H2O gradient+0.05% formic acid) to give pure 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid 2-hydroxy-ethyl ester as a white amorphous solid. The corresponding dihydrochloride was obtained by treatment with a 0.1 M HCl-solution and following lyophilization. Yield: 22 mg MS (ES+): m/e=572, chloro pattern.

Workup

  1. concentrationconcentrated
  2. customunder removed pressure
  3. customThe remaining residue was purified by preparative HPLC (CH3CN/H2O gradient+0.05% formic acid)

Sources & evidence

ORD record
ord-35aa144aeca8424e86d6cddd7c702e59
Source dataset
uspto-grants-2010_06
Patent number
US07741341B2

Reaction notes

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