Diisopropylethylamine → HCID 70816785, Verbindung

HRID 1753913

Reaktionsgleichung

Reaktionsgleichung von HRID 1753913
[CH:1]([C:4]1[C:9]([C:10]([OH:12])=O)=[C:8]([CH3:13])[CH:7]=[C:6]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[N:5]=1)([CH3:3])[CH3:2].C(N(C(C)C)C(C)C)C.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.[NH2:52][CH2:53][C@@H:54]1[CH2:59][CH2:58][CH2:57][CH2:56][C@H:55]1[OH:60]>ClCCl.C(OCC)(=O)C.[Cl-].[NH4+]>[OH:60][C@@H:55]1[CH2:56][CH2:57][CH2:58][CH2:59][C@H:54]1[CH2:53][NH:52][C:10]([C:9]1[C:4]([CH:1]([CH3:2])[CH3:3])=[N:5][C:6]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[CH:7][C:8]=1[CH3:13])=[O:12]

Komponenten

9

Edukt 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2724658trans-2-Aminomethyl-1-cyclohexanolHCID 27960291-Hydroxybenzotriazole hydrateHCID 70817044HCID 70817044, Verbindung

Produkt 1

HCID 70816785HCID 70816785, VerbindungAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 25517Ammonium ChlorideLösungsmittel

Versuchsvorschrift

To a solution of 2-isopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid (synthesized similar to the methods described in sections a) to d) of example X1) (0.20 g, 0.76 mmol) in dichloromethane (15 ml) are added N-ethyl-diisopropylamine (0.32 ml, 0.89 mmol), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.17 g, 0.91 mmol), and 1-hydroxybenzotriazole hydrate (0.02 g, 0.15 mmol). The mixture is stirred for 15 min at RT, and then cooled to 0° C., before (1R,2S)-2-(aminomethyl)cyclohexanol (0.09 g, 0.76 mmol) is added and stirring is continued for 18 h. After completion of the reaction, the mixture is diluted with ethyl acetate and 10% aqueous ammonium chloride. The organic layer is separated and washed with saturated sodium hydrogencarbonate solution and brine, dried over magnesium sulphate and evaporated to dryness. The crude product is purified by flash chromatography (silica gel, 50% ethyl acetate/cyclohexane) to yield N-[[(1S,2R)-2-hydroxy-cyclohexyl]-methyl]-2-isopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide (example X7) (0.18 g, 0.48 mmol, 63%). [M+H]+376.3.

Aufarbeitung

  1. additionis added
  2. stirringstirring
  3. waitis continued for 18 h
  4. customAfter completion of the reaction
  5. customThe organic layer is separated
  6. washwashed with saturated sodium hydrogencarbonate solution and brine
  7. dry with materialdried over magnesium sulphate
  8. customevaporated to dryness
  9. customThe crude product is purified by flash chromatography (silica gel, 50% ethyl acetate/cyclohexane)

Quellen und Nachweise

ORD-Eintrag
ord-eabe245b6376419ebe490432d8fc37e4
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09168259B2

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