HCID 131726655, compound → 4-[[(1-Propyl-1H-imidazol-5-yl)methyl]sulfinyl]benzenamine

HRID 1182357Notes

Reaction equation

HRID 1182357 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 131726655HCID 131726655, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

(S)-4-[[(1-propyl-1H-imidazol-5-yl)methyl]sulfinyl]aniline di-p-toluoyl-D-tartrate monohydrate (494 mg) was dissolved in ethyl acetate (5 ml) and 1 N hydrochloric acid (2.52 ml), followed by separation. To the aqueous layer was added an aqueous 25% potassium carbonate solution (2.52 ml), followed by extraction with 2-propanol-ethyl acetate (1:4) twice. The organic layers were combined, washed with saturated brine and dried over magnesium sulfate, and then the solvent was distilled off under reduced pressure. To the resulting residue was added tetrahydrofuran, and then the solvent was again distilled off under reduced pressure to give (S)-(4-[[(1-propyl-1H-imidazol-5-yl)methyl]sulfinyl]aniline. Then, to a solution of 3-[4-(2-butoxyethoxy)phenyl]-9-isobutyl-8,9-dihydro-7H-pyrido[2,3-b]azepine-6-carboxylic acid (250 mg) in dichloromethane (10 ml) were added a drop of DMF, and then oxalyl chloride (0.065 ml) was added at 0° C. The mixture was returned to room temperature and stirred for 30 minutes under a nitrogen atmosphere, and then the resulting solution was added dropwise to a solution of (S)-(4-[[(1-propyl-1H-imidazol-5-yl)methyl]sulfinyl]aniline and pyridine (1.2 ml) in tetrahydrofuran (10 ml) at 0° C. under a nitrogen atmosphere. The mixture was returned to room temperature and stirred overnight. Then, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with water twice and saturated brine once, and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and then the resultant was separated and purified by basic silica gel column chromatography (ethyl acetate→methanol:ethyl acetate=1:20) to give (S)-3-[4-(2-butoxyethoxy)phenyl]-9-isobutyl-N-[4-[[(1-propyl-1H-imidazol-5-yl)methyl]sulfinyl]aniline]-8,9-dihydro-7H-pyrido[2,3-b]azepine-6-carboxamide (199 mg) (Compound 3) as a yellow amorphous material.

Workup

  1. custom1 N hydrochloric acid (2.52 ml), followed by separation
  2. additionTo the aqueous layer was added an aqueous 25% potassium carbonate solution (2.52 ml)
  3. extractionfollowed by extraction with 2-propanol-ethyl acetate (1:4) twice
  4. washwashed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. additionTo the resulting residue was added tetrahydrofuran
  8. distillationthe solvent was again distilled off under reduced pressure

Sources & evidence

ORD record
ord-70c2fcbf74054eba83e73550b47e7827
Source dataset
uspto-grants-2007_10
Patent number
US07288654B2

Reaction notes

Loading…