Dimethylformamide → HCID 68650048, compound

HRID 1928888Notes

Reaction equation

HRID 1928888 reaction equation
[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[O:25][CH2:24][CH2:23][CH2:22][C:21]([C:26](O)=[O:27])=[CH:20][C:19]=3[CH:29]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].CN(C=O)C.S(Cl)(Cl)=O.[CH3:39][N:40]([CH2:47][C:48]1[CH:54]=[CH:53][C:51]([NH2:52])=[CH:50][CH:49]=1)[CH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1>C1COCC1.O.C(N(CC)CC)C>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[O:25][CH2:24][CH2:23][CH2:22][C:21]([C:26]([NH:52][C:51]4[CH:50]=[CH:49][C:48]([CH2:47][N:40]([CH3:39])[CH:41]5[CH2:46][CH2:45][O:44][CH2:43][CH2:42]5)=[CH:54][CH:53]=4)=[O:27])=[CH:20][C:19]=3[CH:29]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 9877845(4-Amino-benzyl)-methyl-(tetrahydro-pyran-4-yl)-amineHCID 68650364HCID 68650364, compound

Product 1

HCID 68650048HCID 68650048, compoundYield 54.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a solution of 8-[4-(2-butoxyethoxy)phenyl]-3,4-dihydro-2H-1-benzoxocin-5-carboxylic acid (80 mg) in THF (10 ml) were added a drop of DMF and then thionylchloride (0.02 ml) at 0° C. After stirring at room temperature for 30 minutes under a nitrogen atmosphere, the mixture was added to a solution of 4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]aniline (57 mg) and triethylamine (526 mg) in tetrahydrofuran (20 ml) at 0° C. The mixture was stirred at room temperature for 1.5 hours under a nitrogen atmosphere. Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline and dried over magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was separated and purified by silica gel column chromatography (ethyl acetate). Recrystallization from hexane/ethyl acetate gave colorless crystals of 8-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-3,4-dihydro-2H-1-benzoxocin-5-carboxamide (Compound 1, 66 mg).

Workup

  1. customat 0° C
  2. stirringThe mixture was stirred at room temperature for 1.5 hours under a nitrogen atmosphere
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated saline
  5. dry with materialdried over magnesium sulfate
  6. distillationAfter distilling off the solvent under reduced pressure
  7. customthe residue was separated
  8. custompurified by silica gel column chromatography (ethyl acetate)
  9. customRecrystallization from hexane/ethyl acetate

Sources & evidence

ORD record
ord-8bca584d95b34690bb869d3792ab789f
Source dataset
uspto-grants-2012_05
Patent number
US08183273B2

Reaction notes

Loading…