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 586911노트

반응식

HRID 586911 반응식
[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]

참가 물질

9

반응물 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

생성물 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-carboxamide수율 47%

시약·촉매·용매 4

HCID 142844-(Dimethylamino)pyridine촉매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8471Triethylamine용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-74f10461be854e8d874800f232bc244b
출처 데이터셋
uspto-grants-2005_08
특허 번호
US06936602B1

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