Diisopropylethylamine → HCID 178523098, Verbindung

HRID 245763Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 245763
Cl.[NH2:2][CH2:3][C:4]1[C:9]([Cl:10])=[N:8][CH:7]=[CH:6][N:5]=1.[OH:11][C@@H:12]1[CH2:17][CH2:16][C@H:15]([C:18](O)=[O:19])[CH2:14][CH2:13]1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>CN(C)C1C=CN=CC=1.ClCCl>[Cl:10][C:9]1[C:4]([CH2:3][NH:2][C:18]([C@H:15]2[CH2:16][CH2:17][C@@H:12]([OH:11])[CH2:13][CH2:14]2)=[O:19])=[N:5][CH:6]=[CH:7][N:8]=1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 42614233(3-Chloropyrazin-2-yl)methanamine hydrochlorideHCID 178525779HCID 178525779, Verbindung

Produkt 1

HCID 178523098HCID 178523098, VerbindungAusbeute 82,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To 2-aminomethyl-3-chloropyrazine hydrochloride (content 76%, 69.4 mmol, 16.43 g), cis-4-hydroxycyclohexanecarboxylic acid (69.4 mmol, 10 g), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (104 mmol, 19.95 g), 4-dimethylaminopyridine (6.94 mmol, 0.847 g) in dichloromethane (200 ml) was added N,N-diisopropylethylamine (173 mmol, 30.3 ml, 22.41 g) until pH became eight and the reaction mixture was stirred at room temperature for 18 hours. Then it was concentrated in vacuo, ethyl acetate and water were added and the organic layer separated. The water layer was extracted with ethyl acetate twice. The combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (silica gel; dichloromethane with gradient of 0% to 7% methanol). All fractions that contained product were combined and concentrated in vacuo. The residue was dissolved in dichloromethane (400 ml) and washed with 2 M sodium hydroxide (aq) (three times 100 ml), washed with brine, dried (MgSO4) and concentrated in vacuo to give (cis)-N-((3-chloropyrazin-2-yl)methyl)-4-hydroxycyclohexanecarboxamide (15.47 g)

Aufarbeitung

  1. concentrationThen it was concentrated in vacuo, ethyl acetate and water
  2. additionwere added
  3. customthe organic layer separated
  4. extractionThe water layer was extracted with ethyl acetate twice
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (silica gel; dichloromethane with gradient of 0% to 7% methanol)
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue was dissolved in dichloromethane (400 ml)
  11. washwashed with 2 M sodium hydroxide (aq) (three times 100 ml)
  12. washwashed with brine
  13. dry with materialdried (MgSO4)
  14. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-d6d3b03fa2c540ab9f7654c436d98ac2
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658794B2

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