Dimethylformamide → 7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[1-methyl-2-(((1-propylimidazol-5-yl)methyl)sulfanyl)benzimidazol-6-yl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide

HRID 856581Notes

Reaction equation

HRID 856581 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]([CH3:28])[CH3:27])[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.S(Cl)(Cl)=O.[NH2:42][C:43]1[CH:44]=[CH:45][C:46]2[N:50]=[C:49]([S:51][CH2:52][C:53]3[N:57]([CH2:58][CH2:59][CH3:60])[CH:56]=[N:55][CH:54]=3)[N:48]([CH3:61])[C:47]=2[CH:62]=1>O1CCCC1.N1C=CC=CC=1.O>[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]([CH3:27])[CH3:28])[CH2:23][CH2:22][C:21]([C:29]([NH:42][C:43]4[CH:44]=[CH:45][C:46]5[N:50]=[C:49]([S:51][CH2:52][C:53]6[N:57]([CH2:58][CH2:59][CH3:60])[CH:56]=[N:55][CH:54]=6)[N:48]([CH3:61])[C:47]=5[CH:62]=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 24386Thionyl ChlorideHCID 223289057-[4-(2-Butoxyethoxy)phenyl]-1-isobutyl-2,3-dihydro-1-benzazepine-4-carboxylic acidHCID 229388936-Amino-1-methyl-2-(((1-propylimidazol-5-yl)methyl)sulfanyl)benzimidazole

Product 1

HCID 695221267-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[1-methyl-2-(((1-propylimidazol-5-yl)methyl)sulfanyl)benzimidazol-6-yl]-2,3-dihydro-1H-1-benzazepine-4-carboxamideYield 84.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (252 mg) in tetrahydrofuran (10 ml) was added one droplet of DMF. Then, thionyl chloride (0.055 ml) was added to the mixture, and the mixture was stirred for 1 hour under nitrogen atmosphere. This solution was slowly added dropwise to a solution of 6-amino-1-methyl-2-(((1-propylimidazol-5-yl)methyl)sulfanyl)benzimidazole (158 mg) in pyridine (10 ml) at 0° C. under nitrogen atmosphere. The mixture was stirred overnight at room temperature under nitrogen atmosphere, water was added to the mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the obtained residue was purified by basic silica gel column chromatography (hexane:ethyl acetate=1:2→ethyl acetate), to give 7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[1-methyl-2-(((1-propylimidazol-5-yl)methyl)sulfanyl)benzimidazol-6-yl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (319 mg) (Compound 446) as yellow amorphous.

Workup

  1. stirringThe mixture was stirred overnight at room temperature under nitrogen atmosphere
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with water and saturated brine
  4. dry with materialdried over magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe obtained residue was purified by basic silica gel column chromatography (hexane:ethyl acetate=1:2→ethyl acetate)

Sources & evidence

ORD record
ord-6694d6222af84f0f828029f3a52bda1b
Source dataset
uspto-grants-2007_08
Patent number
US07262185B2

Reaction notes

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