1-Hydroxybenzotriazole → 2,3-Dihydro-1-benzoxepine-4-carboxamide

HRID 1277123Notes

Reaction equation

HRID 1277123 reaction equation
N1(C2C=CC([C:13]3[CH:14]=[CH:15][C:16]4[O:22][CH2:21][CH2:20][C:19]([C:23](O)=[O:24])=[CH:18][C:17]=4[CH:26]=3)=CC=2)CCCCC1.C[N:28](CC1C=CC(N)=CC=1)C1CCOCC1.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>[O:22]1[C:16]2[CH:15]=[CH:14][CH:13]=[CH:26][C:17]=2[CH:18]=[C:19]([C:23]([NH2:28])=[O:24])[CH2:20][CH2:21]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 184722357-(4-Piperidinophenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid

Product 1

HCID 184723002,3-Dihydro-1-benzoxepine-4-carboxamideYield 221.6%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 7-(4-piperidinophenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid (0.15 g), 4-(N-methyl-N-(tetrahydropyran-4-yl)aminomethyl)aniline (0.1 g) and 1-hydroxy-benzotriazole (0.07 g) in dimethylformamide (10 ml) was added 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (0.13 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 (0.18 ml), and the mixture was stirred over night. The solvent was evaporated, and to the residue was added water. The mixture 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 to give crude crystals, which were recrystallized from ethyl acetate-hexane to give 7-(4-piperidinophenyl)-N-(4-((N-methyl-N-tetrahydro-pyran-4-yl)amino)methyl)phenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 151) (0.18 g) as colorless crystals.

Workup

  1. temperaturecooling
  2. customThe solvent was evaporated
  3. additionto the residue was added water
  4. extractionThe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with water and saturated sodium chloride solution
  6. dry with materialdried with anhydrous magnesium sulfate
  7. customUnder reduced pressure, the solvent was evaporated
  8. customto give crude crystals, which
  9. customwere recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-2c5237017472474bbefe3d1bdcb21c86
Source dataset
uspto-grants-2000_12
Patent number
US06166006

Reaction notes

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