1-Propanol → Tanogitran

HRID 1593205Notes

Reaction equation

HRID 1593205 reaction equation
Cl.[C:2]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][CH2:12][C:13]2[N:17]([CH3:18])[C:16]3[CH:19]=[CH:20][C:21]([C@@:23]([NH:32][CH2:33][C:34]([O:36]CCC)=[O:35])([C:25]([N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)=[O:26])[CH3:24])=[CH:22][C:15]=3[N:14]=2)=[CH:7][CH:6]=1)(=[NH:4])[NH2:3].C(O)CC.[OH-].[Na+].Cl[Si](C)(C)C>CO.CS(C)=O>[C:2]([C:5]1[CH:6]=[CH:7][C:8]([NH:11][CH2:12][C:13]2[N:17]([CH3:18])[C:16]3[CH:19]=[CH:20][C:21]([C@@:23]([NH:32][CH2:33][C:34]([OH:36])=[O:35])([C:25]([N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)=[O:26])[CH3:24])=[CH:22][C:15]=3[N:14]=2)=[CH:9][CH:10]=1)(=[NH:3])[NH2:4]

Participants

7

Reactant 4

HCID 10311-PropanolHCID 6397ChlorotrimethylsilaneHCID 14798Sodium HydroxideHCID 69248790HCID 69248790, compound

Product 1

HCID 9826322Tanogitran

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent2×

Conditions

Temperature
20 °C

Procedure

To a solution of 93.9 g (0.15 mol) of (R)-2-(4-amidinophenylaminomethyl)-1-methyl-5-[1-(n-propyloxycarbonylmethylamino)-1-(pyrrolidinocarbonyl)-ethyl]-benzimidazole-hydrochloride×1 equivalent n-propanol in 470 mL methanol are added 13.3 g (0.33 mol) of solid sodium hydroxide and this mixture is refluxed for 1.5 hours under an inert gas atmosphere. It is allowed to cool to 50° C. and within 10 minutes 22.8 mL (0.18 mmol) of chlorotrimethylsilan are added dropwise thereto. The mixture is diluted with 470 mL of dimethylsulphoxide and 370 mL of methanol are distilled off at 300 mbar/80° C. To eliminate sodium chloride the suspension is filtered hot. The filtrate is cooled to 20° C. and stirred for 3 hours at 20° C. The suspension formed is suction filtered and the filter cake is washed with 50 mL dimethylsulphoxide and 100 mL acetone. The filter cake is dried at 50° C. in the circulating air drier. The title compound is obtained as a colourless solid.

Workup

  1. temperaturethis mixture is refluxed for 1.5 hours under an inert gas atmosphere
  2. additionare added dropwise
  3. distillationare distilled off at 300 mbar/80° C
  4. filtrationis filtered hot
  5. customThe suspension formed
  6. filtrationfiltered
  7. washthe filter cake is washed with 50 mL dimethylsulphoxide and 100 mL acetone
  8. customThe filter cake is dried at 50° C. in the circulating air drier

Sources & evidence

ORD record
ord-99446fe6442245b8a2bc69797339b739
Source dataset
uspto-grants-2007_11
Patent number
US07294721B2

Reaction notes

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