Potassium Hydroxide → Tanogitran

HRID 1376188Notes

Reaction equation

HRID 1376188 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[C:12]([C:15]1[CH:20]=[CH:19][C:18]([NH:21][CH2:22][C:23]2[N:27]([CH3:28])[C:26]3[CH:29]=[CH:30][C:31]([C@@:33]([NH:42][CH2:43][C:44]([O:46]CC)=[O:45])([C:35]([N:37]4[CH2:41][CH2:40][CH2:39][CH2:38]4)=[O:36])[CH3:34])=[CH:32][C:25]=3[N:24]=2)=[CH:17][CH:16]=1)(=[NH:14])[NH2:13].[OH-].[K+].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[C:12]([C:15]1[CH:16]=[CH:17][C:18]([NH:21][CH2:22][C:23]2[N:27]([CH3:28])[C:26]3[CH:29]=[CH:30][C:31]([C@@:33]([NH:42][CH2:43][C:44]([OH:46])=[O:45])([C:35]([N:37]4[CH2:41][CH2:40][CH2:39][CH2:38]4)=[O:36])[CH3:34])=[CH:32][C:25]=3[N:24]=2)=[CH:19][CH:20]=1)(=[NH:13])[NH2:14]

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 521998p-Toluenesulfonic acid monohydrateHCID 10394778HCID 10394778, compound

Product 1

HCID 9826322Tanogitran

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Conditions

Temperature
40 °C

Procedure

3.7 kg (5.49 mol) of (R)-2-(4-amidinophenylaminomethyl)-1-methyl-5-[1-(ethyloxycarbonylmethylamino)-1-(pyrrolidinocarbonyl)-ethyl]-benzimidazol-p-toluenesulphonic acid salt are dissolved in 7.4 L of methanol at 40° C. To this solution is added a solution of 0.795 kg (12.8 mol) of potassium hydroxide powder in 5.6 L of methanol und this is then rinsed with 1.8 L of methanol. The mixture is stirred for 2.5 hours at 40° C. The potassium salt of the p-toluenesulphonic acid crystallises out. A solution of 1.37 kg (7.2 mol) of p-toluenesulphonic acid monohydrate in 2.8 L of methanol is added to the suspension, this is rinsed with 1.8 litres of methanol and cooled to 22° C. The precipitated potassium salt of p-toluenesulphonic acid is separated off using a pressure filter and the filter cake is washed with 7.4 litres of methanol. The filtrate is inoculated with the title compound and stirred overnight. The precipitated product is suction filtered under argon, washed with 3.7 L of methanol and recycled into the reactor while still damp. 18.5 L of methanol are added and the suspension is refluxed for one hour and cooled to 22° C. The product is suction filtered under argon, washed with 3.7 L of methanol and dried at 30° C. in a circulating air drier. 2.22 kg (85% of theory) of the title compound are obtained.

Workup

  1. washthis is then rinsed with 1.8 L of methanol
  2. customThe potassium salt of the p-toluenesulphonic acid crystallises out
  3. washthis is rinsed with 1.8 litres of methanol
  4. temperaturecooled to 22° C
  5. customThe precipitated potassium salt of p-toluenesulphonic acid is separated off
  6. filtrationfilter
  7. washthe filter cake is washed with 7.4 litres of methanol
  8. stirringstirred overnight
  9. filtrationfiltered under argon
  10. washwashed with 3.7 L of methanol and recycled into the reactor while still damp
  11. addition18.5 L of methanol are added
  12. temperaturethe suspension is refluxed for one hour
  13. temperaturecooled to 22° C
  14. filtrationfiltered under argon
  15. washwashed with 3.7 L of methanol
  16. customdried at 30° C. in a circulating air drier

Sources & evidence

ORD record
ord-d8248222d11b4763bf4710b51890b6a4
Source dataset
uspto-grants-2007_01
Patent number
US07169934B2

Reaction notes

Loading…