1-Hydroxybenzotriazole → 7-[4-(2-butoxyethoxy)phenyl]-1-formyl-N-[4-[(R)-hydroxy(2-pyridyl)methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide

HRID 856421노트

반응식

HRID 856421 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]([CH:25]=[O:26])[CH2:23][CH2:22][C:21]([C:27]([OH:29])=O)=[CH:20][C:19]=3[CH:30]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[NH2:53][C:54]1[CH:59]=[CH:58][C:57]([C@H:60]([C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][N:63]=2)[OH:61])=[CH:56][CH:55]=1>CN(C=O)C.O.C(N(CC)CC)C>[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]([CH:25]=[O:26])[CH2:23][CH2:22][C:21]([C:27]([NH:53][C:54]4[CH:59]=[CH:58][C:57]([C@@H:60]([OH:61])[C:62]5[CH:67]=[CH:66][CH:65]=[CH:64][N:63]=5)=[CH:56][CH:55]=4)=[O:29])=[CH:20][C:19]=3[CH:30]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]

참가 물질

8

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11310163(R)-(4-aminophenyl)-(2-pyridyl) methanolHCID 223290837-[4-(2-butoxyethoxy)phenyl]-1-formyl-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid

생성물 1

HCID 865951737-[4-(2-butoxyethoxy)phenyl]-1-formyl-N-[4-[(R)-hydroxy(2-pyridyl)methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide수율 38.2%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매2회HCID 8471Triethylamine용매

실험 절차

To a solution of 7-[4-(2-butoxyethoxy)phenyl]-1-formyl-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (280 mg) and 1-hydroxybenzotriazole (0.14 g) in DMF (10 ml), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (0.20 g) was added at room temperature, and the mixture was stirred for 0.5 hour. To the reaction solution, a solution of (R)-(4-aminophenyl)-(2-pyridyl) methanol (150 mg) and triethylamine (0.28 ml) in DMF (10 ml) was added dropwise. The mixture was stirred for 3 days at room temperature, water was added to the mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was separated and purified with column chromatography (ethyl acetate) and recrystallized from ethyl acetate-diisopropylether to give 7-[4-(2-butoxyethoxy)phenyl]-1-formyl-N-[4-[(R)-hydroxy(2-pyridyl)methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 76) (154.5 mg) as pale yellow crystals.

후처리

  1. stirringThe mixture was stirred for 3 days at room temperature
  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. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was separated
  7. custompurified with column chromatography (ethyl acetate)
  8. customrecrystallized from ethyl acetate-diisopropylether

출처 및 근거

ORD 기록
ord-1271e5082f5a4da7b018a2e0ec68dfd4
출처 데이터셋
uspto-grants-2007_08
특허 번호
US07262185B2

반응 노트

불러오는 중…