Dimethylformamide → 7-(4-butoxyethoxyphenyl)-1-(2-(2-methyl-1,3-dioxolan-2-yl)acetyl]-N-[4-[[N-methyl-N-(tetrahydropyran-5-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide

HRID 586977Notes

Reaction equation

HRID 586977 reaction equation
CN(C=O)C.[CH3:6][C:7]1([CH2:12][C:13]([OH:15])=O)[O:11][CH2:10][CH2:9][O:8]1.S(Cl)(Cl)=O.[CH2:20]([O:24][CH2:25][CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[CH:35]=[CH:36][C:37]3[NH:43][CH2:42][CH2:41][C:40]([C:44]([NH:46][C:47]4[CH:52]=[CH:51][C:50]([CH2:53][N:54]([CH3:61])[CH:55]5[CH2:60][O:59][CH2:58][CH2:57][CH2:56]5)=[CH:49][CH:48]=4)=[O:45])=[CH:39][C:38]=3[CH:62]=2)=[CH:30][CH:29]=1)[CH2:21][CH2:22][CH3:23]>O1CCCC1.N1C=CC=CC=1>[CH2:20]([O:24][CH2:25][CH2:26][O:27][C:28]1[CH:29]=[CH:30][C:31]([C:34]2[CH:35]=[CH:36][C:37]3[N:43]([C:13](=[O:15])[CH2:12][C:7]4([CH3:6])[O:8][CH2:9][CH2:10][O:11]4)[CH2:42][CH2:41][C:40]([C:44]([NH:46][C:47]4[CH:48]=[CH:49][C:50]([CH2:53][N:54]([CH3:61])[CH:55]5[CH2:60][O:59][CH2:58][CH2:57][CH2:56]5)=[CH:51][CH:52]=4)=[O:45])=[CH:39][C:38]=3[CH:62]=2)=[CH:32][CH:33]=1)[CH2:21][CH2:22][CH3:23]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 5600442-(2-Methyl-1,3-dioxolan-2-yl)acetic acidHCID 223289507-(4-butoxyethoxyphenyl)-N-[4-[[N-methyl-N-(tetrahydropyran-5-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide

Product 1

HCID 701070267-(4-butoxyethoxyphenyl)-1-(2-(2-methyl-1,3-dioxolan-2-yl)acetyl]-N-[4-[[N-methyl-N-(tetrahydropyran-5-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

One droplet of DMF was added to a solution of 2-methyldioxolane-2-ylacetic acid in tetrahydrofuran (10 ml). Then, thionyl chloride (80 mg) was added at 0° C., the temperature was returned to room temperature, and the mixture was stirred under nitrogen atmosphere for 1 hour. This solution was added to a solution of 7-(4-butoxyethoxyphenyl)-N-[4-[[N-methyl-N-(tetrahydropyran-5-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (100 mg) and pyridine (528 mg) in tetrahydrofuran (20 ml) at 0° C. The mixture was stirred under nitrogen atmosphere at room temperature overnight, the insolubles were filtered off using Celite, 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, and the resulting residue was separated and purified with silica gel column chromatography (methanol:ethyl acetate=1:3), which was recrystallized from hexane-ethyl acetate to give 7-(4-butoxyethoxyphenyl)-1-(2-(2-methyl-1,3-dioxolan-2-yl)acetyl]-N-[4-[[N-methyl-N-(tetrahydropyran-5-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (Compound 80) (60 mg) as colorless crystals.

Workup

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

Sources & evidence

ORD record
ord-e3b1dc9af13844e280ad2b79fdd71a55
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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