1-Hydroxybenzotriazole → N-[4-[[methyl(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-(4-morpholinophenyl)-1,1-dioxo-2,3-dihydro-1$l^{6}-benzothiepine-4-carboxamide

HRID 1978551ノート

反応式

HRID 1978551 の反応式
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:14]=[CH:15][C:16]4[S:22](=[O:24])(=[O:23])[CH2:21][CH2:20][C:19]([C:25]([OH:27])=O)=[CH:18][C:17]=4[CH:28]=3)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[CH3:51][N:52]([CH2:59][C:60]1[CH:66]=[CH:65][C:63]([NH2:64])=[CH:62][CH:61]=1)[CH:53]1[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1>CN(C=O)C.CN(C)C1C=CN=CC=1.C(N(CC)CC)C>[CH3:51][N:52]([CH2:59][C:60]1[CH:61]=[CH:62][C:63]([NH:64][C:25]([C:19]2[CH2:20][CH2:21][S:22](=[O:24])(=[O:23])[C:16]3[CH:15]=[CH:14][C:13]([C:10]4[CH:9]=[CH:8][C:7]([N:4]5[CH2:5][CH2:6][O:1][CH2:2][CH2:3]5)=[CH:12][CH:11]=4)=[CH:28][C:17]=3[CH:18]=2)=[O:27])=[CH:65][CH:66]=1)[CH:53]1[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1

参加物

8

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 9877845(4-Amino-benzyl)-methyl-(tetrahydro-pyran-4-yl)-amineHCID 112349537-(4-Morpholinophenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylic acid

生成物 1

HCID 3009393N-[4-[[methyl(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-(4-morpholinophenyl)-1,1-dioxo-2,3-dihydro-1$l^{6}-benzothiepine-4-carboxamide収率 11.9%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒2 回HCID 8471Triethylamine溶媒

実験手順

To a solution of 7-(4-morpholinophenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylic acid (177 mg; purity: about 50%) and 1-hydroxybenzotriazole (HOBt) (90 mg) in DMF (5 ml) was added at room temperature 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (WSC) (127 mg), and the mixture was stirred for 1 hour. To the mixture were added a solution of 4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]aniline (107 mg) and triethylamine (0.12 ml) in DMF (5 ml) and a piece of 4-dimethylaminopyridine, and the mixture was stirred for 64 hours. The mixture was concentrated under reduced pressure, and to the residue was added water. The mixture was extracted with dichloromethane, and the organic layer was washed with saturated brine and dried with magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified with column chromatography (ethanol/ethyl acetate=1:1) and recrystallized from ethanol/diethylether to give yellow crystals of N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-7-(4-morpholinophenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 1) (31.6 mg).

後処理

  1. concentrationThe mixture was concentrated under reduced pressure
  2. additionto the residue was added water
  3. extractionThe mixture was extracted with dichloromethane
  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 residue was purified with column chromatography (ethanol/ethyl acetate=1:1)
  8. customrecrystallized from ethanol/diethylether

出典と根拠

ORDレコード
ord-424cf18ca178448eba0e223a4bc2d739
出典データセット
uspto-grants-2001_05
特許番号
US06235771B1

反応ノート

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