1-Hydroxybenzotriazole → 7-(4-(1-imidazolyl)phenyl)-N-(4-((N-tetra-hydropyran-4-yl-N-methylamino)methyl)phenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide

HRID 565949Notes

Reaction equation

HRID 565949 reaction equation
[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([C:12]3[CH:13]=[CH:14][C:15]4[O:21][CH2:20][CH2:19][C:18]([C:22](O)=[O:23])=[CH:17][C:16]=4[CH:25]=3)=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.[CH3:26][N:27]([CH2:34][C:35]1[CH:41]=[CH:40][C:38]([NH2:39])=[CH:37][CH:36]=1)[CH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.CN(C)C1C=CN=CC=1.C(N(CC)CC)C>[N:1]1([C:6]2[CH:7]=[CH:8][C:9]([C:12]3[CH:13]=[CH:14][C:15]4[O:21][CH2:20][CH2:19][C:18]([C:22]([NH:39][C:38]5[CH:40]=[CH:41][C:35]([CH2:34][N:27]([CH:28]6[CH2:33][CH2:32][O:31][CH2:30][CH2:29]6)[CH3:26])=[CH:36][CH:37]=5)=[O:23])=[CH:17][C:16]=4[CH:25]=3)=[CH:10][CH:11]=2)[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 9877845(4-Amino-benzyl)-methyl-(tetrahydro-pyran-4-yl)-amineHCID 184726247-(4-(1-Imidazolyl)phenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid

Product 1

HCID 184724997-(4-(1-imidazolyl)phenyl)-N-(4-((N-tetra-hydropyran-4-yl-N-methylamino)methyl)phenyl)-2,3-dihydro-1-benzoxepine-4-carboxamideYield 52.6%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 7-(4-(1-imidazolyl)-phenyl)-2,3-dihydro-l-benzoxepine-4-carboxylic acid (0.13g), 4-(N-methyl-N-(tetrahydropyran-4-yl)aminomethyl)aniline (0.11g) and 1-hydroxybenzotriazole (0.07g) in dimethylformamide (20ml) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.13g) under ice-cooling. Under nitrogen atmosphere, the mixture was warmed to room temperature. To the mixture were added 4-dimethylaminopyridine (catalytic amount) and triethylamine (0.2ml), and the mixture was stirred over night. The solvent was evaporated, and the residue was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution and dried with anhydrous magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column (ethyl acetate/methanol/triethylamine) to give crude crystals, which were recrystallized from ethanol-hexane to give 7-(4-(1-imidazolyl)-phenyl)-N-(4-((N-tetra-hydropyran-4-yl-N-methylamino)methyl)-phenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 153) (0.11g) as pale yellow crystals.

Workup

  1. temperaturecooling
  2. customThe solvent was evaporated
  3. extractionthe residue was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated sodium chloride solution
  5. dry with materialdried with anhydrous magnesium sulfate
  6. customUnder reduced pressure, the solvent was evaporated
  7. customthe residue was purified with silica gel column (ethyl acetate/methanol/triethylamine)
  8. customto give crude crystals, which
  9. customwere recrystallized from ethanol-hexane

Sources & evidence

ORD record
ord-7211a8e7fdab4021ac906491a89f4bc1
Source dataset
uspto-grants-2001_01
Patent number
US06172061B2

Reaction notes

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