Hydrochloric Acid → HCID 178511267, Verbindung

HRID 1963870Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1963870
[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5](F)=[N:6][CH:7]=1.[NH2:24][C@H:25]1[CH2:30][CH2:29][C@H:28]([CH2:31][NH:32]C(=O)OC(C)(C)C)[CH2:27][CH2:26]1.Cl.O1CCOCC1>CS(C)=O>[NH2:32][CH2:31][C@H:28]1[CH2:29][CH2:30][C@H:25]([NH:24][C:5]2[CH:4]=[C:3]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=4)[N:10]=3)[C:2]([Cl:1])=[CH:7][N:6]=2)[CH2:26][CH2:27]1

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 66936903HCID 66936903, VerbindungHCID 178453642HCID 178453642, Verbindung

Produkt 1

HCID 178511267HCID 178511267, VerbindungAusbeute 71,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
102.5 °C

Versuchsvorschrift

To 5′-chloro-2′-fluoro-6-(3-fluorobenzyloxy)-2,4′-bipyridine (30 mg, 0.090 mmol) was added DMSO (0.8 ml), TEA (0.025 ml, 0.180 mmol), and tert-butyl (trans-4-aminocyclohexyl)methylcarbamate (41.2 mg, 0.180 mmol). The reaction mixture was flushed with argon and stirred at 100-105° C. for 40 hr. Formation of the intermediate product tert-butyl(trans-4-(5′-chloro-6-(3-fluorobenzyloxy)-2,4′-bipyridin-2′-yl-amino)cyclohexyl)methylcarbamate was indicated by LCMS. (LCMS (m/z): 541.4 (MH+), retention time=1.05 min.). The solvent DMSO was removed under reduce pressure. The Boc group was removed from the intermediate by adding 4M HCl in Dioxane (1.5 ml, 6.00 mmol), followed with stirring at ambient temperature for 90 minutes. The solvent was removed under reduced pressure. The crude product was dissolved in 1.0 ml of DMSO with 0.075 ml of water, filtered and purified by prep LC. After lyophilization, 28.3 mg of the title compound was obtained as a TFA salt. LCMS (m/z): 441.3 (MH+), retention time=0.76 min.; 1H NMR (300 MHz, METHANOL-d4, 25° C.) δ ppm 1.12-1.29 (m, 2 H) 1.29-1.47 (m, 2 H) 1.60-1.76 (m, J=14.76, 7.51, 3.66, 3.66 Hz, 1 H) 1.92 (d, J=12.60 Hz, 2 H) 2.16 (d, J=10.55 Hz, 2 H) 2.84 (d, J=6.74 Hz, 2 H) 3.58-3.71 (m, 1 H) 5.43 (s, 2 H) 6.92-6.99 (m, 2 H) 6.99-7.08 (m, 1 H) 7.18 (d, J=9.67 Hz, 1 H) 7.25 (d, J=7.62 Hz, 1 H) 7.30-7.42 (m, 2 H) 7.83 (t, J=7.77 Hz, 1 H) 8.01 (s, 1 H)

Aufarbeitung

  1. customThe reaction mixture was flushed with argon
  2. customThe solvent DMSO was removed
  3. customThe Boc group was removed from the intermediate
  4. stirringwith stirring at ambient temperature for 90 minutes
  5. customThe solvent was removed under reduced pressure
  6. dissolutionThe crude product was dissolved in 1.0 ml of DMSO with 0.075 ml of water
  7. filtrationfiltered
  8. custompurified by prep LC

Quellen und Nachweise

ORD-Eintrag
ord-80a45448c9424344a97afa32d628bbe6
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08415381B2

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