Acetyl chloride → HCID 86695249, Verbindung

HRID 1504084Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1504084
F[C:2](F)(F)[C:3]([OH:5])=O.[N:8]1([CH:14]2[CH2:19][CH2:18][CH:17]([O:20][C:21]3[C:22]4[C:23]5[CH2:24][NH:25][CH2:26][CH2:27][C:28]=5[S:29][C:30]=4[N:31]=[CH:32][N:33]=3)[CH2:16][CH2:15]2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.C(Cl)(=O)C>C(Cl)Cl>[N:8]1([CH:14]2[CH2:15][CH2:16][CH:17]([O:20][C:21]3[C:22]4[C:23]5[CH2:24][N:25]([C:3](=[O:5])[CH3:2])[CH2:26][CH2:27][C:28]=5[S:29][C:30]=4[N:31]=[CH:32][N:33]=3)[CH2:18][CH2:19]2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1

Komponenten

4

Edukt 2

HCID 6367Acetyl chlorideHCID 86695247HCID 86695247, Verbindung

Produkt 1

HCID 86695249HCID 86695249, VerbindungAusbeute 25,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 3-[[4-(morpholin-4-yl)cyclohexyl]oxy]-8-thia-4,6,12-triazatricyclo[7.4.0.0[2,7]]trideca-1(9),2 (7),3,5-tetraene trifluoroacetate (100 mg, crude) in DCM (20 mL) was added TEA (108 mg, 1.07 mmol). The solution was stirred for 10 min at 0° C. under nitrogen. Then acetyl chloride (41.9 mg, 0.53 mmol) was added to the reaction solution at this temperature and the resulting solution was stirred for 1.5 h at room temperature. The reaction was then quenched by the addition of ethanol and concentrated under vacuum. The crude product was purified by preparative HPLC under the following conditions (Waters): Column: Xbridge Prep C18, 5 μm, 19*50 mm; mobile phase: water with 0.05% NH4HCO3 and CH3CN (10% CH3CN up to 35% in 11 min, up to 95% in 1.5 min, down to 10% in 1.5 min); detector: UV 254/220 nm. After concentration in vacuo and lyophilization overnight, the corresponding 1-(3-[[4-(morpholin-4-yl)cyclohexyl]oxy]-8-thia-4,6,12-triazatricyclo[7.4.0.0[2,7]]trideca-1(9),2(7),3,5-tetraen-12-yl)ethan-1-one (22.1 mg) was obtained as a white solid. MS (ES): m/z 417 (M+H)+ and 429 (M+Na)+. 1H NMR (300 MHz, CD3OD): δ 8.54 (1H, s), 5.33-5.23 (1H, m), 4.91 (2H, s), 3.97, 3.90 (2H, t, t), 3.76-3.69 (4H, m), 3.05, 2.95 (2H, t, t), 2.67-2.58 (4H, t), 2.34-2.25 (3H, m), 2.25, 2.23 (3H, s, s), 2.10 (2H, d), 1.74-1.45 (4H, m).

Aufarbeitung

  1. stirringthe resulting solution was stirred for 1.5 h at room temperature
  2. customThe reaction was then quenched by the addition of ethanol
  3. concentrationconcentrated under vacuum
  4. customThe crude product was purified by preparative HPLC under the following conditions (Waters)
  5. waitmobile phase: water with 0.05% NH4HCO3 and CH3CN (10% CH3CN up to 35% in 11 min
  6. waitup to 95% in 1.5 min
  7. waitdown to 10% in 1.5 min)
  8. concentrationAfter concentration in vacuo and lyophilization overnight

Quellen und Nachweise

ORD-Eintrag
ord-2aacae6fb3b94b7785665ebf77dde11c
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09212190B2

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