Formaldehyde → 5-(5-methyl-1-((2-(4-methylpiperazin-1-yl)pyridin-4-yl) methyl)-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole

HRID 1475188Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1475188
F[C:2](F)(F)C([O-])=O.[CH3:8][C:9]1[N:13]([CH2:14][C:15]2[CH:20]=[CH:19][N:18]=[C:17]([N:21]3[CH2:26][CH2:25][NH2+:24][CH2:23][CH2:22]3)[CH:16]=2)[N:12]=[C:11]([C:27]2[O:31][N:30]=[C:29]([C:32]3[CH:37]=[CH:36][C:35]([O:38][C:39]([F:42])([F:41])[F:40])=[CH:34][CH:33]=3)[N:28]=2)[N:10]=1.C=O.[BH3-]C#N.[Na+]>CCO>[CH3:8][C:9]1[N:13]([CH2:14][C:15]2[CH:20]=[CH:19][N:18]=[C:17]([N:21]3[CH2:26][CH2:25][N:24]([CH3:2])[CH2:23][CH2:22]3)[CH:16]=2)[N:12]=[C:11]([C:27]2[O:31][N:30]=[C:29]([C:32]3[CH:33]=[CH:34][C:35]([O:38][C:39]([F:42])([F:40])[F:41])=[CH:36][CH:37]=3)[N:28]=2)[N:10]=1

Komponenten

5

Edukt 3

HCID 712Formaldehyde2×HCID 5003444Sodium cyanoborohydrideHCID 867118804-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)pyridin-2-yl)piperazin-1-ium 2,2,2-trifluoroacetate

Produkt 1

HCID 732117755-(5-methyl-1-((2-(4-methylpiperazin-1-yl)pyridin-4-yl) methyl)-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazoleAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Versuchsvorschrift

The mixture of 4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)pyridin-2-yl)piperazin-1-ium trifluoroacetate (100 mg, 0.2 mmol), formaldehyde (0.5 mL, 6.0 mmol, 38% in H2O) and paraformaldehyde (100 mg, 3.3 mmol) in EtOH (1 mL) was stirred at RT, then treated with NaBH3CN (63 mg, 1.0 mmol) in one portion. The mixture was stirred at RT for 3 h, and then concentrated under reduced pressure to give the crude product, which was purified by pre-HPLC (Mobile phase: A=10 mM NH4HCO3/H2O, B=MeCN; Gradient: B=60%-95% in 18 min; Column: XBridge C18, 5 um, 30 mm×150 mm) to afford 5-(5-methyl-1-((2-(4-methylpiperazin-1-yl)pyridin-4-yl) methyl)-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole as a white solid (45 mg, 45%). MS (ES+) C23H23F3N8O2 requires: 500. found: 501 [M+H]+; 1H NMR (500 MHz, DMSO-d6) δ 8.22 (d, J=8.3 Hz, 2H), 8.08 (d, J=5.3 Hz, 1H), 7.60 (d, J=8.2 Hz, 2H), 6.77 (s, 1H), 6.42 (d, J=5.3 Hz, 1H), 5.50 (s, 2H), 3.50-3.48 (m, 4H), 2.58 (s, 3H), 2.41-2.32 (m, 4H), 2.20 (s, 3H).

Aufarbeitung

  1. stirringThe mixture was stirred at RT for 3 h
  2. concentrationconcentrated under reduced pressure
  3. customto give the crude product, which
  4. customwas purified by pre-HPLC (Mobile phase

Quellen und Nachweise

ORD-Eintrag
ord-f39751ccb2bd4ad0848715d52da57f95
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09018380B2

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