1-Hydroxybenzotriazole → N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-6-(4-methylphenyl)-2-methylquinoline-3-carboxamide

HRID 1387901Notes

Reaction equation

HRID 1387901 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[N:14]=[C:13]([CH3:18])[C:12]([C:19]([OH:21])=O)=[CH:11]3)=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[CH3:44][N:45]([CH2:52][C:53]1[CH:59]=[CH:58][C:56]([NH2:57])=[CH:55][CH:54]=1)[CH:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1>CN(C=O)C.C(N(CC)CC)C>[CH3:44][N:45]([CH2:52][C:53]1[CH:54]=[CH:55][C:56]([NH:57][C:19]([C:12]2[C:13]([CH3:18])=[N:14][C:15]3[C:10]([CH:11]=2)=[CH:9][C:8]([C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=2)=[CH:17][CH:16]=3)=[O:21])=[CH:58][CH:59]=1)[CH:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]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 229902036-(4-Methylphenyl)-2-methylquinoline-3-carboxylic acid

Product 1

HCID 18472458N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-6-(4-methylphenyl)-2-methylquinoline-3-carboxamideYield 39.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a solution of 6-(4-methylphenyl)-2-methylquinoline-3-carboxylic acid (120 mg) and 1-hydroxy-benzotriazole (88 mg) in DMF (5 ml) was added 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (125 mg) at room temperature, and the mixture was stirred for 2 hours. To the mixture was added a solution of 4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]aniline (105 mg) and triethylamine (0.2 ml) in DMF (5 ml), and the mixture was stirred for 18 hours and concentrated under reduced pressure. To the residue was added water, and the mixture was extracted with chloroform. The organic layer was washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified with column chromatography (ethanol/ethyl acetate=1:2), and recrystallized from ethyl acetate-hexane to give N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-6-(4-methylphenyl)-2-methylquinoline-3-carboxamide (Compound 216) (82 mg) as pale yellow crystals.

Workup

  1. stirringthe mixture was stirred for 18 hours
  2. concentrationconcentrated under reduced pressure
  3. additionTo the residue was added water
  4. extractionthe mixture was extracted with chloroform
  5. washThe organic layer was washed with saturated sodium chloride solution
  6. dry with materialdried with magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was separated
  9. custompurified with column chromatography (ethanol/ethyl acetate=1:2)
  10. customrecrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-4ca557bbb85d4edd92b8ffe4f8f0d670
Source dataset
uspto-grants-2001_07
Patent number
US06268354B1

Reaction notes

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