Dimethylformamide → HCID 22329004, compound

HRID 587096Notes

Reaction equation

HRID 587096 reaction equation
CN([CH:4]=[O:5])C.[CH2:6]([N:8]1[CH:12]=[C:11]([CH2:13][N:14]2[C:20]3[CH:21]=[CH:22][C:23]([C:25]4[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH2:33][CH3:34])=[CH:27][CH:26]=4)=[CH:24][C:19]=3[CH:18]=[C:17]([C:35]([OH:37])=O)[CH2:16][CH2:15]2)[CH:10]=[N:9]1)[CH3:7].S(Cl)(Cl)=O.[CH3:42][N:43]([CH2:50][C:51]1[CH:57]=[CH:56][C:54]([NH2:55])=[CH:53][CH:52]=1)[CH:44]1[CH2:49][CH2:48]OC[CH2:45]1>ClCCl.O.C(N(CC)CC)C>[CH2:6]([N:8]1[CH:12]=[C:11]([CH2:13][N:14]2[C:20]3[CH:21]=[CH:22][C:23]([C:25]4[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH2:33][CH3:34])=[CH:27][CH:26]=4)=[CH:24][C:19]=3[CH:18]=[C:17]([C:35]([NH:55][C:54]3[CH:53]=[CH:52][C:51]([CH2:50][N:43]([CH3:42])[CH:44]4[CH2:45][O:5][CH2:4][CH2:48][CH2:49]4)=[CH:57][CH:56]=3)=[O:37])[CH2:16][CH2:15]2)[CH:10]=[N:9]1)[CH3:7]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 9877845(4-Amino-benzyl)-methyl-(tetrahydro-pyran-4-yl)-amineHCID 22328926HCID 22328926, compound

Product 1

HCID 22329004HCID 22329004, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

One droplet of DMF was added to a solution of 1-[(1-ethylpyrazol-4-yl)methyl]-7-(4-propoxyphenyl)-2,3-dihydro-1-benzazepine-4-carboxylic acid (330 mg) in dichloromethane (15 ml). Then, thionyl chloride (118 mg) was added thereto at 0° C., the temperature was returned to room temperature, and the mixture was stirred for 1 hour under nitrogen atmosphere. Then, this solution was added to a solution of 4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]aniline (219 mg) and triethylamine (2.01 g) in dichloromethane (15 ml) at 0° C. The mixture was stirred at room temperature for overnight under nitrogen atmosphere, water was added thereto, 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=1:4), which was recrystallized from hexane-ethyl acetate to give 1-[(1-ethylpyrazol-4-yl)methyl]-N-[4-[[N-methyl-N-(tetrahydropyran-5-yl)amino]methyl]phenyl]-7-(4-propoxyphenyl)-2,3-dihydro-1-benzazepine-4-carboxamide (362 mg) as yellow crystals.

Workup

  1. customat 0° C.
  2. customwas returned to room temperature
  3. stirringThe mixture was stirred at room temperature for overnight under nitrogen atmosphere
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried with magnesium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customthe resulting residue was separated
  9. custompurified with silica gel column chromatography (methanol:ethyl acetate=1:4), which
  10. customwas recrystallized from hexane-ethyl acetate

Sources & evidence

ORD record
ord-b7fee67feae147cab851b994ce7e3bf3
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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