Dimethylformamide → 8-[4-(2-butoxyethoxy)phenyl]-1-propyl-N-[4-[(N-methyl-N-(tetrahydropyran-4-yl)amino]methyl)phenyl]-1,2,3,4-tetrahydro-1-benzazocine-5-carboxamide

HRID 1810730Notes

Reaction equation

HRID 1810730 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[N:25]([CH2:26][CH2:27][CH3:28])[CH2:24][CH2:23][CH2:22][C:21]([C:29](O)=[O:30])=[CH:20][C:19]=3[CH:32]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].CN(C=O)C.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][O:47][CH2:46][CH2:45]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[N:25]([CH2:26][CH2:27][CH3:28])[CH2:24][CH2:23][CH2:22][C:21]([C:29]([NH:55][C:54]4[CH:53]=[CH:52][C:51]([CH2:50][N:43]([CH3:42])[CH:44]5[CH2:49][CH2:48][O:47][CH2:46][CH2:45]5)=[CH:57][CH:56]=4)=[O:30])=[CH:20][C:19]=3[CH:32]=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 686499298-[4-(2-Butoxyethoxy)phenyl]-1-propyl-1,2,3,4-tetrahydro-1-benzazocine-5-carboxylic acid

Product 1

HCID 686499578-[4-(2-butoxyethoxy)phenyl]-1-propyl-N-[4-[(N-methyl-N-(tetrahydropyran-4-yl)amino]methyl)phenyl]-1,2,3,4-tetrahydro-1-benzazocine-5-carboxamideYield 24.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a solution of 8-[4-(2-butoxyethoxy)phenyl]-1-propyl-1,2,3,4-tetrahydro-1-benzazocine-5-carboxylic acid (180 mg) in THF (10 ml) were added a drop of DMF and then thionylchloride (0.04 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 (118 mg), and triethylamine (1.08 g) in tetrahydrofuran (15 ml) at 0° C. After stirring 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 salt solutions, 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:methanol=8:1) to obtain yellowish amorphous 8-[4-(2-butoxyethoxy)phenyl]-1-propyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,2,3,4-tetrahydro-1-benzazocine-5-carboxamide (Compound 2, 64 mg).

Workup

  1. customat 0° C
  2. stirringAfter stirring 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 salt solutions
  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:methanol=8:1)

Sources & evidence

ORD record
ord-937633d3c92446649ac904e1ee0bd369
Source dataset
uspto-grants-2013_01
Patent number
US08362058B2

Reaction notes

Loading…