Dimethylformamide → (-)-7-[4-(2-butoxyethoxy)phenyl]-1-cyclopropylmethyl-N-[4-[[[1-propylimidazol-5-yl]methyl]sulfinyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide

HRID 856583Notes

Reaction equation

HRID 856583 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:16]=[CH:17][C:18]3[N:24]([CH2:25][CH:26]4[CH2:28][CH2:27]4)[CH2:23][CH2:22][C:21]([C:29](O)=[O:30])=[CH:20][C:19]=3[CH:32]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].CN(C=O)C.C(Cl)(=O)C(Cl)=O.[CH2:44]([N:47]1[C:51]([CH2:52][S:53]([C:55]2[CH:61]=[CH:60][C:58]([NH2:59])=[CH:57][CH:56]=2)=[O:54])=[CH:50][N:49]=[CH:48]1)[CH2:45][CH3:46]>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:16]=[CH:17][C:18]3[N:24]([CH2:25][CH:26]4[CH2:28][CH2:27]4)[CH2:23][CH2:22][C:21]([C:29]([NH:59][C:58]4[CH:57]=[CH:56][C:55]([S:53]([CH2:52][C:51]5[N:47]([CH2:44][CH2:45][CH3:46])[CH:48]=[N:49][CH:50]=5)=[O:54])=[CH:61][CH:60]=4)=[O:30])=[CH:20][C:19]=3[CH:32]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 223292107-[4-(2-butoxyethoxy)phenyl]-1-cyclopropylmethyl-2,3-dihydro-1H-1-benzazepine-4-carboxylic acidHCID 229386104-[[(1-Propyl-1H-imidazol-5-yl)methyl]sulfinyl]benzenamine

Product 1

HCID 69521927(-)-7-[4-(2-butoxyethoxy)phenyl]-1-cyclopropylmethyl-N-[4-[[[1-propylimidazol-5-yl]methyl]sulfinyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

di-p-toluoyl-D-tartarate 1hydrate (894 mg) was dissolved in ethyl acetate (10 ml) and 1N hydrochloric acid (4.6 ml) to separate the layers. To the aqueous layer was added 25% aqueous solution of potassium carbonate (4.6 ml) and the mixture was extracted with 2-propanol-ethyl acetate (1:4) twice. The organic layer was collected, washed with saturated brine, and dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. To the obtained residue was added tetrahydrofuran, and the solvent was distilled off again under reduced pressure to give (−)-4-(((1-propylimidazol-5-yl)methyl)sulfinyl)aniline. Then, to a solution of 7-[4-(2-butoxyethoxy)phenyl]-1-cyclopropylmethyl-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (450 mg) in tetrahydrofuran (10 ml) were added one droplet of DMF and oxalyl chloride (0.12 ml) under nitrogen atmosphere and the mixture was stirred for 30 minutes. This solution was added dropwise to a solution of (−)-4-(((1-propylimidazol-5-yl)methyl)sulfinyl) aniline and pyridine (2.17 ml) in tetrahydrofuran (20 ml) at 0° C. under nitrogen atmosphere. The mixture was allowed to be at room temperature, stirred for 3 hours, and water was added to the mixture, and the mixture was extracted with ethyl-acetate. The organic layer was washed with 10% aqueous solution of acetic acid twice, an aqueous solution of saturated sodium bicarbonate twice and saturated brine once, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was separated and purified by basic silica gel column chromatography (ethyl acetate→ethyl acetate:methanol=50:1), to give (−)-7-[4-(2-butoxyethoxy)phenyl]-1-cyclopropylmethyl-N-[4-[[[1-propylimidazol-5-yl]methyl]sulfinyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (411 mg) (Compound 454) as yellow amorphous.

Workup

  1. customto be at room temperature
  2. stirringstirred for 3 hours
  3. extractionthe mixture was extracted with ethyl-acetate
  4. washThe organic layer was washed with 10% aqueous solution of acetic acid twice
  5. dry with materialan aqueous solution of saturated sodium bicarbonate twice and saturated brine once, and dried over magnesium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe residue was separated
  8. custompurified by basic silica gel column chromatography (ethyl acetate→ethyl acetate:methanol=50:1)

Sources & evidence

ORD record
ord-5f39ed6f6ae249059a648b7583fd5ea0
Source dataset
uspto-grants-2007_08
Patent number
US07262185B2

Reaction notes

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