Triphenylphosphine → 6-[4-[(6-Methylpyridazin-3-yl)oxy]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine

HRID 1675059Notes

Reaction equation

HRID 1675059 reaction equation
CC(OC(/N=N/C(OC(C)C)=O)=O)C.[F:15][C:16]([F:34])([F:33])[C:17]1[N:21]2[N:22]=[C:23]([N:26]3[CH2:31][CH2:30][CH:29]([OH:32])[CH2:28][CH2:27]3)[CH:24]=[CH:25][C:20]2=[N:19][N:18]=1.[CH3:35][C:36]1[CH:37]=[CH:38][C:39](=O)[NH:40][N:41]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[CH3:35][C:36]1[N:41]=[N:40][C:39]([O:32][CH:29]2[CH2:30][CH2:31][N:26]([C:23]3[CH:24]=[CH:25][C:20]4[N:21]([C:17]([C:16]([F:15])([F:33])[F:34])=[N:18][N:19]=4)[N:22]=3)[CH2:27][CH2:28]2)=[CH:38][CH:37]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 833466-methylpyridazin-3(2H)-oneHCID 5363146Diisopropyl azodicarboxylateHCID 245876321-[3-(Trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol

Product 1

HCID 591498106-[4-[(6-Methylpyridazin-3-yl)oxy]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazineYield 12.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

DIAD (0.102 mL, 0.52 mmol) was added to 1-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol (obtained as described in Example 310, preparation of starting materials) (135 mg, 0.47 mmol), 6-methylpyridazin-3(2H)-one (56.9 mg, 0.52 mmol) and triphenylphosphine (136 mg, 0.52 mmol) in THF (5 mL). The resulting solution was stirred at ambient temperature for 3 days. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 2M ammonia in methanol and evaporated to give crude product. The crude 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 afford 6-[4-[(6-methylpyridazin-3-yl)oxy]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (22.00 mg, 12%) as a solid.

Workup

  1. customThe crude product was purified by ion exchange chromatography
  2. washThe desired product was eluted from the column
  3. customevaporated
  4. customto give crude product
  5. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  6. additionFractions containing the desired compound
  7. customwere evaporated to dryness

Sources & evidence

ORD record
ord-9f1d5ab267844aa1ae6cb86894aa495a
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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