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

HRID 586944ノート

反応式

HRID 586944 の反応式
[C:1]([NH:4][CH2:5][C:6]([N:8]1[C:14]2[CH:15]=[CH:16][C:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][CH2:31][CH3:32])=[CH:21][CH:20]=3)=[CH:18][C:13]=2[CH:12]=[C:11]([C:33](O)=[O:34])[CH2:10][CH2:9]1)=[O:7])(=[O:3])[CH3:2].Cl.Cl.[CH3:38][N:39]([CH2:46][C:47]1[CH:53]=[CH:52][C:50]([NH2:51])=[CH:49][CH:48]=1)[CH:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]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>[C:1]([NH:4][CH2:5][C:6]([N:8]1[C:14]2[CH:15]=[CH:16][C:17]([C:19]3[CH:20]=[CH:21][C:22]([O:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][CH2:31][CH3:32])=[CH:23][CH:24]=3)=[CH:18][C:13]=2[CH:12]=[C:11]([C:33]([NH:51][C:50]2[CH:49]=[CH:48][C:47]([CH2:46][N:39]([CH3:38])[CH:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)=[CH:53][CH:52]=2)=[O:34])[CH2:10][CH2:9]1)=[O:7])(=[O:3])[CH3:2]

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 223290341-(N-acetylglycyl)-7-[4-(2-butoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid

生成物 1

HCID 223291241-(N-acetylglycyl)-7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide収率 91.1%

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 1-(N-acetylglycyl)-7-[4-(2-butoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (0.85 g), 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline dihydrochloride (0.52 g) and 1-hydroxybenzotriazole (0.3 g). Under ice-cooling, to the suspension were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1 g), triethylamine (1.7 ml) and 4-dimethylaminopyridine (catalytic amount), and the mixture was stirred at room temperature overnight. The solvent was evaporated and, to the residue was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified with basic silica gel column chromatography (ethyl acetate/methanol/triethylamine) to give 1-(N-acetylglycyl)-7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (1.1 g) as pale yellow amorphous.

後処理

  1. temperatureUnder ice-cooling, to the suspension
  2. customThe solvent was evaporated and, to the residue
  3. additionwas added water
  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 basic silica gel column chromatography (ethyl acetate/methanol/triethylamine)

出典と根拠

ORDレコード
ord-6cf9b00732954c46b9def4b7dd5b6e4a
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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