Acetohydrazide → Tert-butyl 1-(4-(2-acetylhydrazinecarbonyl)-6-fluoro-3-(pyridin-2-yl)quinolin-2-yl)ethylcarbamate

HRID 1616064Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1616064
[C:1]([O:5][C:6]([NH:8][CH:9]([C:11]1[C:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)=[C:19]([C:27](O)=[O:28])[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([F:30])[CH:17]=2)[N:12]=1)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:31]([NH:34][NH2:35])(=[O:33])[CH3:32].Cl.CN(C)CCCN=C=NCC.N1C2C(=NC=CC=2)N(O)N=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CN(C=O)C>[C:31]([NH:34][NH:35][C:27]([C:19]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([F:30])[CH:17]=2)[N:12]=[C:11]([CH:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH3:10])[C:20]=1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1)=[O:28])(=[O:33])[CH3:32]

Komponenten

8

Edukt 5

HCID 14039AcetohydrazideHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 596346802-(1-(Tert-butoxycarbonylamino)ethyl)-6-fluoro-3-(pyridin-2-yl)quinoline-4-carboxylic acid

Produkt 1

HCID 67595345Tert-butyl 1-(4-(2-acetylhydrazinecarbonyl)-6-fluoro-3-(pyridin-2-yl)quinolin-2-yl)ethylcarbamate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of 2-(1-(tert-butoxycarbonylamino)ethyl)-6-fluoro-3-(pyridin-2-yl)quinoline-4-carboxylic acid (2.011 g, 4.89 mmol) and acetic hydrazide (0.543 g, 7.33 mmol) in DCM (10.99 mL) and DMF (1.222 mL) was treated 0° C. with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl) (2.81 g, 14.66 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (HOAt) (1.995 g, 14.66 mmol), and sodium bicarbonate (1.232 g, 14.66 mmol) successively at 0° C. Then the reaction was stirred at rt. After 15 h, the reaction was partitioned between DCM (100 mL) and 1.0 M aq LiCl (100 mL). The separated aq layer was extracted with DCM (1×100 mL) and the combined organic extracts were washed with 1.0 M aq LiCl (100 mL), dried over MgSO4 and concentrated in vacuo. The crude material was purified by silica gel column chromatography eluting with a gradient of 0% to 50% EtOAc in hexane, to provide tert-butyl 1-(4-(2-acetylhydrazinecarbonyl)-6-fluoro-3-(pyridin-2-yl)quinolin-2-yl)ethylcarbamate as off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 10.44 (1H, s), 9.81 (1H, s), 8.69 (1H, d, J=4.7 Hz), 8.37 (1H, dd, J=10.4, 2.7 Hz), 8.16 (1H, dd, J=9.2, 5.5 Hz), 7.93 (1H, td, J=7.7, 1.8 Hz), 7.77 (1H, td, J=8.8, 2.7 Hz), 7.56 (1H, d, J=7.6 Hz), 7.47 (1H, dd, J=7.0, 5.3 Hz), 7.02 (1H, d, J=7.6 Hz), 4.70-4.82 (1H, m), 1.87 (3H, s), 1.31 (9H, s), 1.22 (3H, d, J=6.7 Hz); LC-MS (ESI) m/z 468.1 [M+H]+.

Aufarbeitung

  1. customthe reaction was partitioned between DCM (100 mL) and 1.0 M aq LiCl (100 mL)
  2. extractionThe separated aq layer was extracted with DCM (1×100 mL)
  3. washthe combined organic extracts were washed with 1.0 M aq LiCl (100 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by silica gel column chromatography
  7. washeluting with a gradient of 0% to 50% EtOAc in hexane

Quellen und Nachweise

ORD-Eintrag
ord-559b5bbbe6d0400ca23b7b3a7cc4f9be
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765768B2

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