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 1978551Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1978551
[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

Komponenten

8

Edukt 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

Produkt 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-carboxamideAusbeute 11,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6228DimethylformamideLösungsmittel2×HCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-424cf18ca178448eba0e223a4bc2d739
Quelldatensatz
uspto-grants-2001_05
Patentnummer
US06235771B1

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