Piperidine → [8-Methyl-3-(1-{4-[5-(piperidin-1-ylcarbonyl)pyridin-2-yl]phenyl}cyclopropyl)-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl]methanol

HRID 1424134Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1424134
[OH:1][CH2:2][C:3]1([CH3:31])[S:9][CH2:8][CH2:7][N:6]2[C:10]([C:13]3([C:16]4[CH:21]=[CH:20][C:19]([C:22]5[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][N:23]=5)=[CH:18][CH:17]=4)[CH2:15][CH2:14]3)=[N:11][N:12]=[C:5]2[CH2:4]1.[NH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1.Cl.C(N=C=NCCCN(C)C)C.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH3:31][C:3]1([CH2:2][OH:1])[S:9][CH2:8][CH2:7][N:6]2[C:10]([C:13]3([C:16]4[CH:21]=[CH:20][C:19]([C:22]5[CH:30]=[CH:29][C:25]([C:26]([N:32]6[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]6)=[O:27])=[CH:24][N:23]=5)=[CH:18][CH:17]=4)[CH2:14][CH2:15]3)=[N:11][N:12]=[C:5]2[CH2:4]1

Komponenten

6

Edukt 4

HCID 8082PiperidineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 867129516-(4-{1-[8-(Hydroxymethyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-3-yl]cyclopropyl}phenyl)nicotinic acid

Produkt 1

HCID 86712979[8-Methyl-3-(1-{4-[5-(piperidin-1-ylcarbonyl)pyridin-2-yl]phenyl}cyclopropyl)-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl]methanolAusbeute 11,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of the compound (200 mg, 0.458 mmol) obtained in Example 66, piperidine (210 μL, 2.29 mmol), N,N-dimethylaminopyridine (6 mg, 46 μmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (264 mg, 1.37 mmol) in N,N-dimethylformamide (4.00 mL) was stirred at room temperature for 6 h. Saturated aqueous sodium hydrogencarbonate (100 mL) was added to the reaction mixture, the mixture was extracted with dichloromethane/2-propanol (4/1), and the organic layer was washed with water and dried with anhydrous sodium sulfate. Then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=9:1 to 4:1) to obtain the title compound (26 mg, 11%) as a white solid.

Aufarbeitung

  1. extractionthe mixture was extracted with dichloromethane/2-propanol (4/1)
  2. washthe organic layer was washed with water
  3. dry with materialdried with anhydrous sodium sulfate
  4. distillationThen the solvent was distilled off under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (ethyl acetate:methanol=9:1 to 4:1)

Quellen und Nachweise

ORD-Eintrag
ord-9b1c882d78f14ef6b5ef109f7f50c200
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08927536B2

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