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 1928889노트

반응식

HRID 1928889 반응식
[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]

참가 물질

8

반응물 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

생성물 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-carboxamide수율 24.3%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회HCID 8471Triethylamine용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-7f6896e201f9467fa9d9e4d66f0b0a94
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08183273B2

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