1-Hydroxybenzotriazole → HCID 178423665, compound

HRID 1169413Notes

Reaction equation

HRID 1169413 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[CH2:17][CH2:16][CH2:15][C:14]([C:18](O)=[O:19])=[CH:13][C:12]=3[CH:21]=2)=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.Cl.[CH3:46][N:47]([CH2:54][C@H:55]1[CH2:60][CH2:59][C@H:58]([NH2:61])[CH2:57][CH2:56]1)[CH:48]1[CH2:53][CH2:52][O:51][CH2:50][CH2:49]1.C1CCN2C(=NCCC2)CC1>C(#N)C.C(N(CC)CC)C>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[CH2:17][CH2:16][CH2:15][C:14]([C:18]([NH:61][C@H:58]4[CH2:57][CH2:56][C@H:55]([CH2:54][N:47]([CH3:46])[CH:48]5[CH2:53][CH2:52][O:51][CH2:50][CH2:49]5)[CH2:60][CH2:59]4)=[O:19])=[CH:13][C:12]=3[CH:21]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 105886612-(4-methylphenyl)-6,7-dihydro-5H-benzocycloheptene-8-carboxylic acidHCID 178484107HCID 178484107, compound

Product 1

HCID 178423665HCID 178423665, compoundYield 72.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8471TriethylamineSolvent

Procedure

Into a suspension of 2-(4-methylphenyl)-6,7-dihydro-5H-benzocycloheptene-8-carboxylic acid (200 mg) and 1-hydroxybenzotriazole (146 mg) in acetonitrile (10 ml) was added at room temperature 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (207 mg), and the resulting mixture was stirred for 2 hours. Into the reaction mixture was added a solution of trans-4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]cyclohexylamine dihydrochloride (323 mg), 1,8-diazabicyclo[5,4,0]-7-undecene (326 mg) and triethylamine (0.2 ml) in acetonitrile (15 ml), and the resulting mixture was stirred for 10 hours. After the reaction mixture was concentrated under reduced pressure, water was added to the residue, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with an aqueous saturated solution of sodium chloride and was dried with anhydrous magnesium sulfate. The resulting organic layer was evaporated under reduced pressure to remove the solvent and the residue was then subjected to purification using column chromatography (ethanol/ethyl acetate 1:1) and to recrystallization (ethyl acetate/hexane) to obtain trans-2-(4-methylphenyl)-N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]cyclohexyl]-6,7-dihydro-5H-benzocycloheptene-8-carboxamide (compound 64) (253 mg) as colorless crystals.

Workup

  1. stirringthe resulting mixture was stirred for 10 hours
  2. concentrationAfter the reaction mixture was concentrated under reduced pressure, water
  3. additionwas added to the residue
  4. extractionthe resulting mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with an aqueous saturated solution of sodium chloride
  6. dry with materialwas dried with anhydrous magnesium sulfate
  7. customThe resulting organic layer was evaporated under reduced pressure
  8. customto remove the solvent
  9. customthe residue was then subjected to purification
  10. customto recrystallization (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-e85e0a0cb2584335b5ee281a52c7a74f
Source dataset
uspto-grants-2003_09
Patent number
US06627651B1

Reaction notes

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