1-Hydroxybenzotriazole → 7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-1-(4-sulfamoylphenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxamide

HRID 586912ノート

反応式

HRID 586912 の反応式
[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]([C:25]4[CH:30]=[CH:29][C:28]([S:31](=[O:34])(=[O:33])[NH2:32])=[CH:27][CH:26]=4)[CH2:23][CH2:22][C:21]([C:35](O)=[O:36])=[CH:20][C:19]=3[CH:38]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].Cl.Cl.[CH3:41][N:42]([CH2:49][C:50]1[CH:56]=[CH:55][C:53]([NH2:54])=[CH:52][CH:51]=1)[CH:43]1[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C=O)C.CN(C)C1C=CN=CC=1.C(N(CC)CC)C>[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]([C:25]4[CH:26]=[CH:27][C:28]([S:31](=[O:34])(=[O:33])[NH2:32])=[CH:29][CH:30]=4)[CH2:23][CH2:22][C:21]([C:35]([NH:54][C:53]4[CH:55]=[CH:56][C:50]([CH2:49][N:42]([CH3:41])[CH:43]5[CH2:48][CH2:47][O:46][CH2:45][CH2:44]5)=[CH:51][CH:52]=4)=[O:36])=[CH:20][C:19]=3[CH:38]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4]

参加物

8

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 111505194-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline dihydrochlorideHCID 223292437-[4-(2-butoxyethoxy)phenyl]-1-(4-sulfamoylphenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid

生成物 1

HCID 223292127-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-1-(4-sulfamoylphenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxamide収率 41.2%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒HCID 8471Triethylamine溶媒

実験手順

In DMF (20 ml) were suspended 7-[4-(2-butoxyethoxy)phenyl]-1-(4-sulfamoylphenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (0.15 g), 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline dihydrochloride (0.11 g) and 1-hydroxybenzotriazole (0.06 g). Under ice-cooling, to the suspension were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.16 g), triethylamine (0.2 ml) and 4-dimethylaminopyridine (catalytic amount), and the mixture was stirred at room temperature overnight, The solvent was evaporated, water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried with anhydrous magnesium sulfate, and the solvent was evaporated. The residue was purified with silica gel column (ethyl acetate/methanol/triethylamine) to give crude crystals, which were recrystallized from ethyl acetate-hexane to give 7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-1-(4-sulfamoylphenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 46) (0.085 g) as yellow crystals.

後処理

  1. temperatureUnder ice-cooling, to the suspension
  2. customThe solvent was evaporated
  3. additionwater was added to the residue
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with water and saturated brine
  6. dry with materialdried with anhydrous magnesium sulfate
  7. customthe solvent was evaporated
  8. customThe residue was purified with silica gel column (ethyl acetate/methanol/triethylamine)
  9. customto give crude crystals, which
  10. customwere recrystallized from ethyl acetate-hexane

出典と根拠

ORDレコード
ord-49c8fca56ebb4e949a1d805cabe6b1bb
出典データセット
uspto-grants-2005_08
特許番号
US06936602B1

反応ノート

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