Pyridine → HCID 69027928, Verbindung

HRID 489617Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 489617
[C:1]([O:5][C:6]([N:8]([CH2:16][C:17]1[CH:18]=[C:19]([CH:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[CH:20]=[CH:21][CH:22]=1)[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:29]([O:33][C:34]([NH:36][C:37]1[CH:38]=[N:39][CH:40]=[C:41]([CH:45]=1)[C:42](O)=[O:43])=[O:35])([CH3:32])([CH3:31])[CH3:30].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.N1C=CC=CC=1>CN(C)C=O.C(OCC)(=O)C>[C:29]([O:33][C:34](=[O:35])[NH:36][C:37]1[CH:38]=[N:39][CH:40]=[C:41]([C:42]([N:26]2[CH2:25][CH2:24][CH:23]([C:19]3[CH:20]=[CH:21][CH:22]=[C:17]([CH2:16][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH:18]=3)[CH2:28][CH2:27]2)=[O:43])[CH:45]=1)([CH3:32])([CH3:30])[CH3:31]

Komponenten

8

Edukt 5

HCID 1049PyridineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 222661545-[(tert-Butoxycarbonyl)amino]pyridine-3-carboxylic acidHCID 222661574-[3-(N,N-di-tert-butoxycarbonylaminomethyl)phenyl]piperidine

Produkt 1

HCID 69027928HCID 69027928, VerbindungAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a 0° C. solution of 4-{3-[N,N-bis-(tert-butoxycarbonyl)aminomethyl]-phenyl}-piperidine (0.1545 g, 0.3956 mmol, EXAMPLE 1B), 5-tert-butoxycarbonylamino-nicotinic acid (0.0966 g, 0.4055 mmol), 1-hydroxy-7-azabenzotriazole (0.0290 g, 0.2131 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.1500 g, 0.7824 mmol) in dimethylformamide (5.0 mL) was added pyridine (0.065 mL, 0.8037 mmol). The reaction mixture was stirred 30 minutes at 0° C., then allowed to warm to room temperature under inert atmosphere. After 16 hours at ambient temperature the reaction solution was diluted with ethyl acetate (30 mL), washed with saturated ammonium chloride (2×15 mL), saturated sodium bicarbonate (15 mL), and brine (15 mL). The organic phase was dried over magnesium sulfate, filtered, and evaporated to dryness. The residue was purified by silica gel chromatography eluting with a mixture of ethyl acetate and methylene chloride (1:1, v/v) to give {5-[1-(4-{3-[N,N-bis-(tert-butoxycarbonyl)aminomethyl]-phenyl}-piperidin-1-yl)methanoyl]-pyridin-3-yl}carbamic acid tert-butyl ester as a colorless oil (0.1812 g): TLC, 50:50-methylene chloride:ethyl acetate, Rf=0.20. 1H NMR (300 MHz, CDCl3) δ 8.67 (d, J=2.6 Hz, 1H), 8.34 (d, J=1.4 Hz, 1H), 8.09 (s, 1H), 7.93 (s, 1H), 7.21-7.35 (m, 1H), 7.08-7.18 (m, 3H), 4.81-4.93 (m, 1H), 4.78 (s, 2H), 3.81-3.93 (br m, 1H), 3.11-3.28 (br m, 1H), 2.70-2.96 (m, 2H), 1.51 (s, 9H), 1.45 (s, 18H), 1.40-2.02 (m partially obscured, 4H); 13C NMR (75 MHz, CDCl3) δ 167.5, 152.6, 152.5, 144.8, 141.3, 141.0, 138.9, 135.7, 131.8, 128.5, 125.6, 125.3, 125.2, 124.1, 82.4, 81.0, 77.2, 49.3, 42.5, 28.1, 27.8; MS (CI) m/z 611 (M+H).

Aufarbeitung

  1. temperatureto warm to room temperature under inert atmosphere
  2. washwashed with saturated ammonium chloride (2×15 mL), saturated sodium bicarbonate (15 mL), and brine (15 mL)
  3. dry with materialThe organic phase was dried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with a mixture of ethyl acetate and methylene chloride (1:1

Quellen und Nachweise

ORD-Eintrag
ord-c24eb77e781d4f798ec1867436ec7c4d
Quelldatensatz
uspto-grants-2005_12
Patentnummer
US06977263B2

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