Triphenylphosphine → 6-[4-[4-[2-(1-methyl-1H-pyrazol-5-yl)ethoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine

HRID 1675104

Reaktionsgleichung

Reaktionsgleichung von HRID 1675104
CC(OC(/N=N/C(OC(C)C)=O)=O)C.[F:15][C:16]([F:40])([F:39])[C:17]1[N:21]2[N:22]=[C:23]([N:26]3[CH2:31][CH2:30][CH:29]([C:32]4[CH:37]=[CH:36][C:35]([OH:38])=[CH:34][CH:33]=4)[CH2:28][CH2:27]3)[CH:24]=[CH:25][C:20]2=[N:19][N:18]=1.[CH3:41][N:42]1[C:46]([CH2:47][CH2:48]O)=[CH:45][CH:44]=[N:43]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.C(Cl)Cl>[CH3:41][N:42]1[C:46]([CH2:47][CH2:48][O:38][C:35]2[CH:36]=[CH:37][C:32]([CH:29]3[CH2:30][CH2:31][N:26]([C:23]4[CH:24]=[CH:25][C:20]5[N:21]([C:17]([C:16]([F:15])([F:39])[F:40])=[N:18][N:19]=5)[N:22]=4)[CH2:27][CH2:28]3)=[CH:33][CH:34]=2)=[CH:45][CH:44]=[N:43]1

Komponenten

7

Edukt 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 218324192-(1-methyl-1H-pyrazol-5-yl)ethan-1-olHCID 367300784-(1-(3-(Trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl)phenol

Produkt 1

HCID 426358766-[4-[4-[2-(1-methyl-1H-pyrazol-5-yl)ethoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

DIAD (3.70 mL, 18.77 mmol) was added to 4-(1-(3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl)phenol (6.2 g, 17.06 mmol), 2-(1-methyl-1H-pyrazol-5-yl)ethanol (2.368 g, 18.77 mmol) and triphenylphosphine (4.92 g, 18.77 mmol) in THF (150 mL) under nitrogen. The resulting solution was stirred at ambient temperature for 1 day. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 2M NH3/MeOH and pure fractions were evaporated to dryness to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to afford crude product. Product was dissolved in DCM (100 mL) and washed with 2M NaOH (100 mL) twice. Organic layer was evaporated to afford 6-(4-(4-(2-(1-methyl-1H-pyrazol-5-yl)ethoxy)phenyl)piperidin-1-yl)-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine anhydrous Form A (4.95 g, 61.5%) as a white solid.

Aufarbeitung

  1. customThe crude product was purified by ion exchange chromatography
  2. washThe desired product was eluted from the column
  3. customwere evaporated to dryness
  4. customto afford crude product
  5. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in DCM
  6. customPure fractions were evaporated to dryness
  7. customto afford crude product
  8. washwashed with 2M NaOH (100 mL) twice
  9. customOrganic layer was evaporated

Quellen und Nachweise

ORD-Eintrag
ord-b9064c1891b74b61b956f806ed6ce0a2
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003649B2

Verknüpfte Notizen

Wird geladen…