Dimethylformamide → HCID 9939875, compound

HRID 586970Notes

Reaction equation

HRID 586970 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[C:32]([CH3:37])=[N:33][O:34][C:35]=4[CH3:36])[CH2:28][CH2:27][C:26]([C:38](O)=[O:39])=[CH:25][C:24]=3[CH:41]=2)=[CH:16][CH:15]=1)[CH2:7][CH2:8][CH3:9].S(Cl)(Cl)=O.[CH3:46][N:47]([CH2:54][C:55]1[CH:61]=[CH:60][C:58]([NH2:59])=[CH:57][CH:56]=1)[CH:48]1[CH2:53][CH2:52][O:51][CH2:50][CH2:49]1>O1CCCC1.O.C(N(CC)CC)C>[CH2:6]([O:10][CH2:11][CH2:12][O:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]2[CH:21]=[CH:22][C:23]3[N:29]([CH2:30][C:31]4[C:32]([CH3:37])=[N:33][O:34][C:35]=4[CH3:36])[CH2:28][CH2:27][C:26]([C:38]([NH:59][C:58]4[CH:60]=[CH:61][C:55]([CH2:54][N:47]([CH3:46])[CH:48]5[CH2:53][CH2:52][O:51][CH2:50][CH2:49]5)=[CH:56][CH:57]=4)=[O:39])=[CH:25][C:24]=3[CH:41]=2)=[CH:18][CH:19]=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 69749809HCID 69749809, compound

Product 1

HCID 9939875HCID 9939875, compoundYield 22.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

One droplet of DMF was added to a solution of 7-(4-butoxyethoxyphenyl)-1-[(3,5-dimethylisoxazol-4-yl)methyl]-2,3-dihydro-1-benzazepine-4-carboxylic acid (140 mg) in tetrahydrofuran (1 ml). Then, thionyl chloride (102 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 (690 mg) in tetrahydrofuran (25 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 silica gel column chromatography (methanol:ethyl acetate=1:3) to give 7-(4-butoxyethoxyphenyl)-1-[(3,5-dimethylisoxazol-4-yl)methyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (Compound 71) (45 mg) as yellow amorphous.

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 silica gel column chromatography (methanol:ethyl acetate=1:3)

Sources & evidence

ORD record
ord-6227c2de7d564260bb21c5bb9def081d
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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