Diisopropylethylamine → 4-(1-(3-(Trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl)phenol

HRID 1675098Notes

Reaction equation

HRID 1675098 reaction equation
CCN(C(C)C)C(C)C.Cl[C:11]1[CH:12]=[CH:13][C:14]2[N:15]([C:17]([C:20]([F:23])([F:22])[F:21])=[N:18][N:19]=2)[N:16]=1.Cl.[NH:25]1[CH2:30][CH2:29][CH:28]([C:31]2[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][CH:32]=2)[CH2:27][CH2:26]1>CN(C=O)C>[F:21][C:20]([F:23])([F:22])[C:17]1[N:15]2[N:16]=[C:11]([N:25]3[CH2:30][CH2:29][CH:28]([C:31]4[CH:32]=[CH:33][C:34]([OH:37])=[CH:35][CH:36]=4)[CH2:27][CH2:26]3)[CH:12]=[CH:13][C:14]2=[N:19][N:18]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 6136576-Chloro-3-(trifluoromethyl)-(1,2,4)triazolo(4,3-b)pyridazineHCID 242507534-Piperidin-4-ylphenol, HCl

Product 1

HCID 367300784-(1-(3-(Trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl)phenolYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

DIPEA (5.84 mL, 33.54 mmol) was added to 6-chloro-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine (2.99 g, 13.41 mmol) and 4-(piperidin-4-yl)phenol hydrochloride (CAS 263139-27-1, 3.01 g, 14.08 mmol) in DMF (30 mL). The resulting solution was stirred at 80° C. for 1 hour. The mixture was cooled to room temperature, evaporated to dryness and re-dissolved in DCM (200 mL). The solution was washed with water (200 mL) and saturated brine (200 mL), dried over MgSO4 and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 50 to 70% ethyl acetate in isohexane. Pure fractions were evaporated to dryness to afford 4-[1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenol (4.47 g, 92%) as a solid.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customevaporated to dryness
  3. dissolutionre-dissolved in DCM (200 mL)
  4. washThe solution was washed with water (200 mL) and saturated brine (200 mL)
  5. dry with materialdried over MgSO4
  6. customevaporated
  7. customto afford crude product
  8. customThe crude product was purified by flash silica chromatography, elution gradient 50 to 70% ethyl acetate in isohexane
  9. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-76583e875fed401eafe30655cbf57c04
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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