1-Hydroxybenzotriazole → HCID 18472272, compound

HRID 1277117Notes

Reaction equation

HRID 1277117 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:15]=[CH:16][C:17]4[O:23][CH2:22][CH2:21][C:20]([C:24](O)=[O:25])=[CH:19][C:18]=4[CH:27]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[CH3:28][N:29]([CH2:36][C:37]1[CH:43]=[CH:42][C:40]([NH2:41])=[CH:39][CH:38]=1)[CH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]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]1[CH2:3][CH2:4][N:5]([C:8]2[CH:9]=[CH:10][C:11]([C:14]3[CH:15]=[CH:16][C:17]4[O:23][CH2:22][CH2:21][C:20]([C:24]([NH:41][C:40]5[CH:39]=[CH:38][C:37]([CH2:36][N:29]([CH:30]6[CH2:35][CH2:34][O:33][CH2:32][CH2:31]6)[CH3:28])=[CH:43][CH:42]=5)=[O:25])=[CH:19][C:18]=4[CH:27]=3)=[CH:12][CH:13]=2)[CH2:6][CH2:7]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 18472598HCID 18472598, compound

Product 1

HCID 18472272HCID 18472272, compoundYield 80.4%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 7-(4-(4-methylpiperazin-1-yl)phenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid (0.12 g), 4-(N-methyl-N-(tetrahydropyran-4-yl)aminomethyl)aniline (0.08 g) and 1-hydroxybenzotriazole(0.05 g) in dimethylformamide (15 ml) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydro-chloride (0.1 g), under ice-cooling. Under nitrogen atmosphere, the mixture was cooled to room temperature. To the mixture were added 4-dimethylaminopyridine (catalytic amount) and triethylamine (0.14 ml), and the mixture was stirred overnight. 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 7-(4-(4-methylpiperazin-1-yl)phenyl)-N-(4-((N-tetrahydropyran-4-yl-N-methylamino)methyl)phenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 124) (0.15 g) as colorless crystals.

Workup

  1. temperatureunder ice-cooling
  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-1c5fbc5396834aaf91ece836e2912160
Source dataset
uspto-grants-2000_12
Patent number
US06166006

Reaction notes

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