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

HRID 2381133Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2381133
CC(OC(/N=N/C(OC(C)C)=O)=O)C.[OH:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2([OH:41])[CH2:27][CH2:26][N:25]([C:28]3[CH:29]=[CH:30][C:31]4[N:32]([C:34]([C:37]([F:40])([F:39])[F:38])=[N:35][N:36]=4)[N:33]=3)[CH2:24][CH2:23]2)=[CH:18][CH:17]=1.[CH3:42][N:43]1[C:47]([CH2:48][CH2:49]OC2C=CC(C3CCN(C4CCC5N(C(C(F)(F)F)=NN=5)N=4)CC3)=CC=2)=[CH:46][CH:45]=[N:44]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[CH3:42][N:43]1[C:47]([CH2:48][CH2:49][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3([OH:41])[CH2:27][CH2:26][N:25]([C:28]4[CH:29]=[CH:30][C:31]5[N:32]([C:34]([C:37]([F:40])([F:39])[F:38])=[N:35][N:36]=5)[N:33]=4)[CH2:24][CH2:23]3)=[CH:18][CH:17]=2)=[CH:46][CH:45]=[N:44]1

Komponenten

6

Edukt 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 468938506-[4-[4-[2-(1-methyl-1H-pyrazol-5-yl)ethoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazineHCID 667887034-(4-Hydroxyphenyl)-1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol

Produkt 1

HCID 441259734-[4-[2-(1-methyl-1H-pyrazol-5-yl)ethoxy]phenyl]-1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-olAusbeute 72,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

DIAD (0.311 mL, 1.58 mmol) was added dropwise to 4-(4-hydroxyphenyl)-1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol (500 mg, 1.32 mmol), 2-(1-methyl-1H-pyrazol-5-yl)ethanol (obtained as described in Example 15, preparation of starting materials) (249 mg, 1.98 mmol) and triphenylphosphine (519 mg, 1.98 mmol) in THF (10 mL) under nitrogen. The resulting suspension was stirred at ambient temperature for 16 hours then the solvents were evaporated to give crude product. The crude product was purified by flash silica chromatography, eluting with EtOAc then a gradient of 3 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to give a solid which was triturated with ether, filtered and dried to give 4-[4-[2-(1-methyl-1H-pyrazol-5-yl)ethoxy]phenyl]-1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol (464 mg, 72.2%) as a solid.

Aufarbeitung

  1. customthe solvents were evaporated
  2. customto give crude product
  3. customThe crude product was purified by flash silica chromatography
  4. washeluting with EtOAc
  5. customPure fractions were evaporated to dryness
  6. customto give a solid which
  7. customwas triturated with ether
  8. filtrationfiltered
  9. customdried

Quellen und Nachweise

ORD-Eintrag
ord-9a05e7d1b59646a8a824bef815393ca6
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08258140B2

Notizen zur Reaktion

Wird geladen…