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 402221ノート

反応式

HRID 402221 の反応式
[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]

参加物

8

反応物 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

生成物 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-carboxamide収率 24.3%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8471Triethylamine溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-90a5b6293adb4929b491413adfec0345
出典データセット
uspto-grants-2014_06
特許番号
US08741943B2

反応ノート

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