4-(((1-Propylimidazol-5-yl)methyl)sulfinyl)aniline di-p-toluoyl-D-tartarate monohydrate → 4-[[(1-Propyl-1H-imidazol-5-yl)methyl]sulfinyl]benzenamine

HRID 2222795Notes

Reaction equation

HRID 2222795 reaction equation
O.C1(C)C=CC(C([C@](C(O)=O)(O)[C@](C(C2C=CC(C)=CC=2)=O)(O)C(O)=O)=O)=CC=1.[CH2:30]([N:33]1[C:37]([CH2:38][S:39]([C:41]2[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=2)=[O:40])=[CH:36][N:35]=[CH:34]1)[CH2:31][CH3:32]>C(OCC)(=O)C>[CH2:30]([N:33]1[C:37]([CH2:38][S:39]([C:41]2[CH:42]=[CH:43][C:44]([NH2:45])=[CH:46][CH:47]=2)=[O:40])=[CH:36][N:35]=[CH:34]1)[CH2:31][CH3:32]

Participants

3

Reactant 1

HCID 1317268664-(((1-Propylimidazol-5-yl)methyl)sulfinyl)aniline di-p-toluoyl-D-tartarate monohydrate

Product 1

HCID 229386104-[[(1-Propyl-1H-imidazol-5-yl)methyl]sulfinyl]benzenamine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

(−)-4-(((1-Propylimidazol-5-yl)methyl)sulfinyl)aniline di-p-toluoyl-D-tartarate monohydrate (905 mg) was dissolved in ethyl acetate (10 ml) and 1N hydrochloric acid (4.76 ml), followed by separation. To the aqueous layer was added an aqueous 25% potassium carbonate solution (4.76 ml), followed by extraction with 2-propanol-ethyl acetate (1:4) three times. The organic layers were combined and washed with saturated brine, dried with magnesium sulfate, and the solvent was distilled off under reduced pressure. To the resulting residue was added tetrahydrofuran, after which the solvent was distilled off again under reduced pressure to give (−)-4-(((1-propylimidazol-5-yl)methyl)sulfinyl)aniline. Then, to a solution of 10-(4-(2-butoxyethoxy)phenyl)-1-isobutyl-1,2,3,4,5,6-hexahydro-1-benzoazetin-7-carboxylic acid (500 mg) in tetrahydrofuran (10 ml) was added a drop of DMF, and then thionyl chloride (0.099 ml) was added, and the mixture was stirred under nitrogen atmosphere for 30 minutes. The resulting solution was added dropwise to the tetrahydrofuran (10 ml) solution of (−)-4-(((1-propylimidazol-5-yl)methyl)sulfinyl)aniline and triethylamine (1.9 ml) at 0° C. under nitrogen atmosphere. The mixture was returned to room temperature and stirred for 3 hours, after which water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with 10% aqueous acetic acid solution twice, with aqueous saturated sodium bicarbonate solution twice, and with saturated brine once, after which the resultant was dried with magnesium sulfate. After distilling off the solvent under reduced pressure, the resultant was separated and purified with a basic silica gel column chromatography (hexane:ethyl acetate=1:4→ethyl acetate) to give (−)-10-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[4-[[[1-propylimidazol-5-yl]methyl]sulfinyl]phenyl]-1,2,3,4,5,6-hexahydro-1-benzoazetin-7-carboxamide (135 mg) (Compound 28) as a yellow amorphous material.

Workup

  1. custom1N hydrochloric acid (4.76 ml), followed by separation
  2. additionTo the aqueous layer was added an aqueous 25% potassium carbonate solution (4.76 ml)
  3. extractionfollowed by extraction with 2-propanol-ethyl acetate (1:4) three times
  4. washwashed with saturated brine
  5. dry with materialdried with magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. additionTo the resulting residue was added tetrahydrofuran
  8. distillationafter which the solvent was distilled off again under reduced pressure

Sources & evidence

ORD record
ord-bfeb6c2677ce47dc8fc8997df49c6da6
Source dataset
uspto-grants-2008_05
Patent number
US07371772B2

Reaction notes

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