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

HRID 586911ノート

反応式

HRID 586911 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[N:26]=[C:27]([CH3:30])[S:28][CH:29]=4)[CH2:23][CH2:22][C:21]([C:31]([OH:33])=O)=[CH:20][C:19]=3[CH:34]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].Cl.Cl.[CH3:37][N:38]([CH2:45][C:46]1[CH:52]=[CH:51][C:49]([NH2:50])=[CH:48][CH:47]=1)[CH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C=O)C.CN(C)C1C=CN=CC=1.O.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[N:26]=[C:27]([CH3:30])[S:28][CH:29]=4)[CH2:23][CH2:22][C:21]([C:31]([NH:50][C:49]4[CH:51]=[CH:52][C:46]([CH2:45][N:38]([CH3:37])[CH:39]5[CH2:44][CH2:43][O:42][CH2:41][CH2:40]5)=[CH:47][CH:48]=4)=[O:33])=[CH:20][C:19]=3[CH:34]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4]

参加物

9

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 223290877-[4-(2-butoxyethoxy)phenyl]-1-(2-methylthiazol-4-yl)-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid

生成物 1

HCID 98747097-[4-(2-butoxyethoxy)phenyl]-1-(2-methylthiazol-4-yl)-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide収率 47%

試薬・触媒・溶媒 4

HCID 142844-(Dimethylamino)pyridine触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8471Triethylamine溶媒

実験手順

In DMF (20 ml) were suspended 7-[4-(2-butoxyethoxy)phenyl]-1-(2-methylthiazol-4-yl)-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (0.13 g), 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline dihydrochloride (0.1 g) and 1-hydroxybenzotriazole (0.06 g). Under ice-cooling, to the suspension were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.15 g), triethylamine (0.18 ml) and 4-dimethylaminopyridine (catalytic amount), and the mixture was stirred at room temperature overnight, which was poured into water and 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-diethyl ether-hexane to give 7-[4-(2-butoxyethoxy)phenyl]-1-(2-methylthiazol-4-yl)-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 45) (0.087 g) as pale yellow crystals.

後処理

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

出典と根拠

ORDレコード
ord-74f10461be854e8d874800f232bc244b
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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