Dimethylformamide → (S)-3-[4-(2-butoxyethoxy)phenyl]-10-isobutyl-N-[4-[[(1-propyl-1H-imidazol-5-yl)methyl]sulfinyl]phenyl]-7,8,9,10-tetrahydropyrido[2,3-b]azocine-6-carboxamide

HRID 1182354Notes

Reaction equation

HRID 1182354 reaction equation
[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:33]=[N:32][C:18]3[N:19]([CH2:28][CH:29]([CH3:31])[CH3:30])[CH2:20][CH2:21][CH2:22][C:23]([C:25](O)=[O:26])=[CH:24][C:17]=3[CH:16]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].CN(C=O)C.C(Cl)(=O)C(Cl)=O.[CH2:45]([N:48]1[C:52]([CH2:53][S@@:54]([C:56]2[CH:62]=[CH:61][C:59]([NH2:60])=[CH:58][CH:57]=2)=[O:55])=[CH:51][N:50]=[CH:49]1)[CH2:46][CH3:47]>ClCCl.O1CCCC1.O.N1C=CC=CC=1>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:33]=[N:32][C:18]3[N:19]([CH2:28][CH:29]([CH3:31])[CH3:30])[CH2:20][CH2:21][CH2:22][C:23]([C:25]([NH:60][C:59]4[CH:61]=[CH:62][C:56]([S@:54]([CH2:53][C:52]5[N:48]([CH2:45][CH2:46][CH3:47])[CH:49]=[N:50][CH:51]=5)=[O:55])=[CH:57][CH:58]=4)=[O:26])=[CH:24][C:17]=3[CH:16]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 11308257(S)-4-(((1-Propyl-1H-imidazol-5-yl)methyl)sulfinyl)anilineHCID 694246853-[4-(2-Butoxyethoxy)phenyl]-10-isobutyl-7,8,9,10-tetrahydropyrido[2,3-b]azocine-6-carboxylic acid

Product 1

HCID 69425862(S)-3-[4-(2-butoxyethoxy)phenyl]-10-isobutyl-N-[4-[[(1-propyl-1H-imidazol-5-yl)methyl]sulfinyl]phenyl]-7,8,9,10-tetrahydropyrido[2,3-b]azocine-6-carboxamide

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

(S)-4-(((1-propylimidazol-5-yl)methyl)sulfinyl)aniline di-p-toluoyl-D-tartrate monohydrate (479 mg) was dissolved in ethyl acetate (5 ml) and 1 N hydrochloric acid (2.44 ml), followed by separation. To the aqueous layer was added an aqueous 25% potassium carbonate solution (2.44 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-propylimidazol-5-yl)methyl)sulfinyl)aniline. Then, to a solution of 3-[4-(2-butoxyethoxy)phenyl]-10-isobutyl-7,8,9,10-tetrahydropyrido[2,3-b]azocine-6-carboxylic acid (250 mg) in dichloromethane (10 ml) were added a drop of DMF, and then oxalyl chloride (0.063 ml) 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-propylimidazol-5-yl)methyl)sulfinyl)aniline and pyridine (1.16 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 residue was separated and purified by basic silica gel column chromatography (ethyl acetate→methanol:ethyl acetate=3:100) to give (S)-3-[4-(2-butoxyethoxy)phenyl]-10-isobutyl-N-[4-[[(1-propyl-1H-imidazol-5-yl)methyl]sulfinyl]phenyl]-7,8,9,10-tetrahydropyrido[2,3-b]azocine-6-carboxamide (294 mg) (Compound 1) as a yellow amorphous material.

Workup

  1. customat 0° C
  2. customwas returned to room temperature
  3. customwas returned to room temperature
  4. stirringstirred overnight
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with water twice
  7. dry with materialsaturated brine once, and then dried over magnesium sulfate
  8. distillationThe solvent was distilled off under reduced pressure
  9. customthe residue was separated
  10. custompurified by basic silica gel column chromatography (ethyl acetate→methanol:ethyl acetate=3:100)

Sources & evidence

ORD record
ord-491572691aca49829e1e6281e96b1bd4
Source dataset
uspto-grants-2007_10
Patent number
US07288654B2

Reaction notes

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