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 1675097

Reaktionsgleichung

Reaktionsgleichung von HRID 1675097
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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:60][N:61]1[C:65]([CH2:66][CH2:67]O)=[CH:64][CH:63]=[N:62]1>C1COCC1>[CH3:60][N:61]1[C:65]([CH2:66][CH2:67][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:64][CH:63]=[N:62]1

Komponenten

6

Edukt 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 218324192-(1-methyl-1H-pyrazol-5-yl)ethan-1-ol2×HCID 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]pyridazineAusbeute 52 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

DIAD (78 μl, 0.386 mmol) was added dropwise to 4-[1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenol (117 mg, 0.322 mmol), triphenylphosphine (101 mg, 0.386 mmol) and 2-(1-methyl-1H-pyrazol-5-yl)ethanol (obtained as described in PCT Int. Appl. WO 2007017222, Intermediate 1) (49 mg, 0.386 mmol) in THF (2 mL). The resulting mixture was stirred at ambient temperature for 16 hours and then added to a SCX column. The crude product was eluted using 2M ammonia in methanol and the product-containing fractions were evaporated. The product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to give 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 (79 mg, 52%) as a solid.

Aufarbeitung

  1. additionadded to a SCX column
  2. washThe crude product was eluted
  3. customthe product-containing fractions were evaporated
  4. customThe product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  5. additionFractions containing the desired compound
  6. customwere evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-9f1c52c1b0304af4a315f4ab4e700e64
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003649B2

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