Trifluoroacetic acid → HCID 86695247, Verbindung

HRID 1504083Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1504083
[N:1]1([CH:7]2[CH2:12][CH2:11][CH:10]([O:13][C:14]3[C:15]4[CH:22]=[C:21]([CH2:23][CH2:24][NH:25][C:26](=O)OC(C)(C)C)[S:20][C:16]=4[N:17]=[CH:18][N:19]=3)[CH2:9][CH2:8]2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[F:33][C:34]([F:39])([F:38])[C:35]([OH:37])=[O:36]>C(Cl)Cl.O>[F:33][C:34]([F:39])([F:38])[C:35]([OH:37])=[O:36].[N:1]1([CH:7]2[CH2:12][CH2:11][CH:10]([O:13][C:14]3[C:15]4[C:22]5[CH2:26][NH:25][CH2:24][CH2:23][C:21]=5[S:20][C:16]=4[N:17]=[CH:18][N:19]=3)[CH2:9][CH2:8]2)[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1

Komponenten

4

Edukt 2

HCID 6422Trifluoroacetic acidHCID 86695246HCID 86695246, Verbindung

Produkt 1

HCID 86695247HCID 86695247, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21908982Water methylene chlorideLösungsmittel

Versuchsvorschrift

To a solution of tert-butyl N-[2-(4-[[4-(morpholin-4-yl)cyclohexyl]oxy]thieno[2,3-d]pyrimidin-6-yl)ethyl]carbamate (150 mg, 0.32 mmol, 1.00 equiv) in DCM/H2O (10/0.5 mL) was added trifluoroacetic acid (0.8 mL) at 0° C. and stirred overnight at room temperature. After concentration under vacuum, the residue was dissolved in DCE (30 mL) and paraformaldehyde (180 mg) and trifluoroacetic acid (1 mL) were added. The resulting solution was stirred overnight at 45° C. under nitrogen. After concentration under vacuum, the residue was purified by preparative HPLC under the following conditions: Column: XBridge Shield RP18 OBD, 5 μm, 19*150 mm; mobile phase: water (with 0.5% TFA) and CH3CN (0% CH3CN up to 21% in 12 min, up to 95% in 2 min, down to 0% in 2 min); flow rate: 20 mL/min; UV detection at 254/220 nm. After concentration under vacuum, the desired 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) was obtained as a light yellow solid. MS (ES): m/z 375 (M+H)+.

Aufarbeitung

  1. concentrationAfter concentration under vacuum
  2. dissolutionthe residue was dissolved in DCE (30 mL)
  3. additionparaformaldehyde (180 mg) and trifluoroacetic acid (1 mL) were added
  4. stirringThe resulting solution was stirred overnight at 45° C. under nitrogen
  5. concentrationAfter concentration under vacuum
  6. customthe residue was purified by preparative HPLC under the following conditions
  7. waitmobile phase: water (with 0.5% TFA) and CH3CN (0% CH3CN up to 21% in 12 min
  8. waitup to 95% in 2 min
  9. waitdown to 0% in 2 min)
  10. concentrationAfter concentration under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-17ad39b5cb9f4830b4bd44eb37f41500
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09212190B2

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