Triethylamine → HCID 178454040, Verbindung

HRID 724272Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 724272
[C:1]([O:5][C:6](=[O:15])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[F:23][C:24]1[CH:25]=[N:26][C:27]([Cl:33])=[C:28]([CH:32]=1)[C:29](O)=[O:30].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[C:1]([O:5][C:6](=[O:15])[NH:7][C@H:8]1[CH2:9][CH2:10][C@@H:11]([NH:14][C:29]([C:28]2[C:27]([Cl:33])=[N:26][CH:25]=[C:24]([F:23])[CH:32]=2)=[O:30])[CH2:12][CH2:13]1)([CH3:4])([CH3:2])[CH3:3]

Komponenten

7

Edukt 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2756050Cis tert-Butyl 4-aminocyclohexylcarbamateHCID 114352432-Chloro-5-fluoronicotinic acid

Produkt 1

HCID 178454040HCID 178454040, VerbindungAusbeute 73,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

(4-Amino-cyclohexyl)-carbamic acid tert-butyl ester (80:20 syn:anti, 4.49 g, 20.9 mmol) was dissolved in dimethylformamide (100 ml) and triethylamine (8.34 ml, 59.8 mmol) was added followed by 5-fluoro-2-chloronicotinic acid (3.5 g, 19.9 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (4.2 g, 21.9 mmol) and 1-hydroxybenzotriazole (2.96 g, 21.9 mmol). The reaction was stirred under nitrogen at room temperature for 18 h and the solvent was removed under reduced pressure. The residue was partitioned between sat. sodium bicarbonate solution (50 ml) and ethyl acetate (100 ml) and the aqueous phase was extracted with dichloromethane (2×50 ml). The combined organic extracts were concentrated under reduced pressure, re-dissolved in dichloromethane (100 ml), washed with water (50 ml), dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of ethyl acetate:pentane (2:3 changing to 1:1, by volume) to give {cis-4-[(2-Chloro-5-fluoro-pyridine-3-carbonyl)-amino]-cyclohexyl}-carbamic acid tert-butyl ester (5.44 g) as a white foam.

Aufarbeitung

  1. customthe solvent was removed under reduced pressure
  2. customThe residue was partitioned between sat. sodium bicarbonate solution (50 ml) and ethyl acetate (100 ml)
  3. extractionthe aqueous phase was extracted with dichloromethane (2×50 ml)
  4. concentrationThe combined organic extracts were concentrated under reduced pressure
  5. dissolutionre-dissolved in dichloromethane (100 ml)
  6. washwashed with water (50 ml)
  7. dry with materialdried over MgSO4
  8. customthe solvent was removed under reduced pressure
  9. customThe residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of ethyl acetate:pentane (2:3 changing to 1:1, by volume)

Quellen und Nachweise

ORD-Eintrag
ord-0fe66ae5d12047f8a2b3a2023b4f7275
Quelldatensatz
uspto-grants-2006_11
Patentnummer
US07141586B2

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