1-Hydroxybenzotriazole → HCID 10626473, compound

HRID 1387904Notes

Reaction equation

HRID 1387904 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:14]=[CH:15][C:16]4[CH2:22][CH2:21][CH2:20][C:19]([C:23]([OH:25])=O)=[CH:18][C:17]=4[CH:26]=3)=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:27][N:28]([CH2:35][C:36]1[CH:42]=[CH:41][C:39]([NH2:40])=[CH:38][CH:37]=1)[CH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.C(N(CC)CC)C>[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:14]=[CH:15][C:16]4[CH2:22][CH2:21][CH2:20][C:19]([C:23]([NH:40][C:39]5[CH:41]=[CH:42][C:36]([CH2:35][N:28]([CH:29]6[CH2:34][CH2:33][O:32][CH2:31][CH2:30]6)[CH3:27])=[CH:37][CH:38]=5)=[O:25])=[CH:18][C:17]=4[CH:26]=3)=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 9877845(4-Amino-benzyl)-methyl-(tetrahydro-pyran-4-yl)-amineHCID 10593775HCID 10593775, compound

Product 1

HCID 10626473HCID 10626473, compoundYield 61.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 2-(4-piperidinophenyl)-6,7-dihydro-5H-benzocycloheptene-8-carboxylic acid (0.45 g), 4-(N-methyl-N-(tetrahydropyran-4-yl)aminomethyl)aniline (0.31 g) and 1-hydroxybenzotriazole (0.18 g) in dimethylformamide (20 ml) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydro-chloride (0.37 g) under ice-cooling. Under nitrogen atmosphere, the mixture was warmed to room temperature. To the mixture were added 4-dimethyl-aminopyridine (catalytic amount) and triethylamine (0.54 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, and the residue was purified with silica gel column (ethyl acetate/methanol/triethylamine) to give crude crystals, which were recrystallized from ethyl acetate-hexane to give 2-(4-piperidinophenyl)-N-(4-((N-tetrahydropyran-4-yl-N-methylamino)methyl)phenyl)-6,7-dihydro-5H-benzocyclo-hepten-8-carboxamide (Compound 224) (0.44 g) as pale orange 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. customthe residue was purified with silica gel column (ethyl acetate/methanol/triethylamine)
  9. customto give crude crystals, which
  10. customwere recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-c58b15fbfe0741ecb515312440559ab5
Source dataset
uspto-grants-2001_07
Patent number
US06268354B1

Reaction notes

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