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

HRID 856420Notes

Reaction equation

HRID 856420 reaction equation
[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]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11481070(S)-(4-aminophenyl)-(2-pyridyl) methanolHCID 223290837-[4-(2-butoxyethoxy)phenyl]-1-formyl-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid

Product 1

HCID 865951727-[4-(2-butoxyethoxy)phenyl]-1-formyl-N-[4-[(S)-hydroxy(2-pyridyl)methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamideYield 61%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent

Procedure

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 1 hour. To the reaction solution, a solution of (S)-(4-aminophenyl)-(2-pyridyl) methanol (150 mg) and triethylamine (0.28 ml) in DMF (10 ml) were added dropwise. The mixture was stirred for 4 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 by column chromatography (ethyl acetate) and recrystallized from ethyl acetate-diisopropylether to give 7-[4-(2-butoxyethoxy)phenyl]-1-formyl-N-[4-[(S)-hydroxy(2-pyridyl)methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 75) (247 mg) as pale yellow crystals.

Workup

  1. stirringThe mixture was stirred for 4 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 by column chromatography (ethyl acetate)
  8. customrecrystallized from ethyl acetate-diisopropylether

Sources & evidence

ORD record
ord-8edacb9341a142719c3648e8556a5d47
Source dataset
uspto-grants-2007_08
Patent number
US07262185B2

Reaction notes

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