1-Hydroxybenzotriazole → 7-(4-dimethylaminophenyl)-N-(4-((1-oxophosphorinan-1-yl)methyl)phenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide

HRID 2228143Notes

Reaction equation

HRID 2228143 reaction equation
[CH3:1][N:2]([CH3:23])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[CH:11][C:12]3[O:18][CH2:17][CH2:16][C:15]([C:19](O)=[O:20])=[CH:14][C:13]=3[CH:22]=2)=[CH:5][CH:4]=1.[NH2:24][C:25]1[CH:38]=[CH:37][C:28]([CH2:29][P:30]2(=[O:36])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)=[CH:27][CH:26]=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>[CH3:1][N:2]([CH3:23])[C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:10]=[CH:11][C:12]3[O:18][CH2:17][CH2:16][C:15]([C:19]([NH:24][C:25]4[CH:26]=[CH:27][C:28]([CH2:29][P:30]5(=[O:36])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]5)=[CH:37][CH:38]=4)=[O:20])=[CH:14][C:13]=3[CH:22]=2)=[CH:7][CH:8]=1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 184725407-(4-Dimethylaminophenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acidHCID 229899861-(4-Aminobenzyl)phosphorinane-1-oxide

Product 1

HCID 184722457-(4-dimethylaminophenyl)-N-(4-((1-oxophosphorinan-1-yl)methyl)phenyl)-2,3-dihydro-1-benzoxepine-4-carboxamideYield 72.1%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 7—(4-dimethylaminophenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid (0.1 g), 1—(4-aminobenzyl)phosphorinane-1-oxide (0.08 g) and 1-hydroxybenzotriazole (0.05 g) in dimethylformamide (7 ml) was added l-ethyl-3—(3-dimethylaminopropyl)carbodiimide hydrochloride (0.1 g) under ice-cooling. Under nitrogen atmosphere, the mixture was warmed to room temperature. To the mixture were added 4-dimethylaminopyridine (catalytic amount) and triethylamine (0.15 ml), 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 water and 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-dimethylaminophenyl)-N-(4—((1-oxophosphorinan-1-yl)methyl)phenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 154) (0.12 g) as colorless crystals.

Workup

  1. temperaturecooling
  2. customThe solvent was evaporated
  3. extractionthe residue was extracted with ethyl acetate
  4. washThe organic layer was washed with water and 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-a16e79a89016414880afe5f834fafb03
Source dataset
uspto-grants-2002_07
Patent number
US06413947B1

Reaction notes

Loading…