Dimethylformamide → 7-(4-butoxyethoxyphenyl)-1-[(1-methylimidazol-2-yl)methyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide

HRID 586966Notes

Reaction equation

HRID 586966 reaction equation
CN(C=O)C.[CH2:6]([O:10][CH2:11][CH2:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:21]=[CH:22][C:23]3[N:29]([CH2:30][C:31]4[N:32]([CH3:36])[CH:33]=[CH:34][N:35]=4)[CH2:28][CH2:27][C:26]([C:37]([OH:39])=O)=[CH:25][C:24]=3[CH:40]=2)=[CH:16][CH:15]=1)[CH2:7][CH2:8][CH3:9].S(Cl)(Cl)=O.[CH3:45][N:46]([CH2:53][C:54]1[CH:60]=[CH:59][C:57]([NH2:58])=[CH:56][CH:55]=1)[CH:47]1[CH2:52][CH2:51][O:50][CH2:49][CH2:48]1>O1CCCC1.O.C(N(CC)CC)C>[CH2:6]([O:10][CH2:11][CH2:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:21]=[CH:22][C:23]3[N:29]([CH2:30][C:31]4[N:32]([CH3:36])[CH:33]=[CH:34][N:35]=4)[CH2:28][CH2:27][C:26]([C:37]([NH:58][C:57]4[CH:59]=[CH:60][C:54]([CH2:53][N:46]([CH3:45])[CH:47]5[CH2:52][CH2:51][O:50][CH2:49][CH2:48]5)=[CH:55][CH:56]=4)=[O:39])=[CH:25][C:24]=3[CH:40]=2)=[CH:16][CH:15]=1)[CH2:7][CH2:8][CH3:9]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 9877845(4-Amino-benzyl)-methyl-(tetrahydro-pyran-4-yl)-amineHCID 69749859HCID 69749859, compound

Product 1

HCID 30094177-(4-butoxyethoxyphenyl)-1-[(1-methylimidazol-2-yl)methyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamideYield 32.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

One droplet of DMF was added to a solution of 7-(4-butoxyethoxyphenyl)-1-[(1-methylimidazol-2-yl)methyl]-2,3-dihydro-1-benzazepine-4-carboxylic acid (140 mg) in tetrahydroturan (10 ml). Then, thionyl chloride (41 mg) was added at 0° C., the temperature was returned to room temperature, and the mixture was stirred under nitrogen atmosphere for 1 hour. Then, this mixture was added to a solution of 4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]aniline (75 mg) and triethylamine (346 mg) in tetrahydrofuran (30 ml) at 0° C. The suspension was stirred under nitrogen atmosphere at room temperature overnight, to the mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried with magnesium sulfate. The solvent was evaporated under reduced pressure, the resulting residue was separated and purified with basic silica gel column chromatography (ethyl acetate), which was recrystallized from hexane-ethyl acetate to give 7-(4-butoxyethoxyphenyl)-1-[(1-methylimidazol-2-yl)methyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (Compound 67) (65 mg) as yellow crystals.

Workup

  1. customwas returned to room temperature
  2. stirringThe suspension was stirred under nitrogen atmosphere at room temperature overnight, to the mixture
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried with magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe resulting residue was separated
  8. custompurified with basic silica gel column chromatography (ethyl acetate), which
  9. customwas recrystallized from hexane-ethyl acetate

Sources & evidence

ORD record
ord-242b0b32c5c74f40b7ede7e8526f6a0f
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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