Trifluoroacetic acid → 4-[[4-[3-(Trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperazin-1-yl]methyl]aniline

HRID 1675033Notes

Reaction equation

HRID 1675033 reaction equation
C(O)(C(F)(F)F)=O.[F:8][C:9]([F:41])([F:40])[C:10]1[N:14]2[N:15]=[C:16]([N:19]3[CH2:24][CH2:23][N:22]([CH2:25][C:26]4[CH:31]=[CH:30][C:29]([NH:32]C(=O)OC(C)(C)C)=[CH:28][CH:27]=4)[CH2:21][CH2:20]3)[CH:17]=[CH:18][C:13]2=[N:12][N:11]=1>C(Cl)Cl>[F:41][C:9]([F:8])([F:40])[C:10]1[N:14]2[N:15]=[C:16]([N:19]3[CH2:20][CH2:21][N:22]([CH2:25][C:26]4[CH:31]=[CH:30][C:29]([NH2:32])=[CH:28][CH:27]=4)[CH2:23][CH2:24]3)[CH:17]=[CH:18][C:13]2=[N:12][N:11]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67339893HCID 67339893, compound

Product 1

HCID 591497504-[[4-[3-(Trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperazin-1-yl]methyl]anilineYield 56.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (0.5 mL, 0.15 mmol) was added to tert-butyl N-[4-[[4-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperazin-1-yl]methyl]phenyl]carbamate (obtained as described in Example 146, 72 mg, 0.15 mmol) in DCM (2 mL). The resulting solution was stirred at ambient temperature for 2 hours and then evaporated to dryness. The crude product was purified by preparative HPLC using decreasingly polar mixtures of water (containing 0.1% TFA) and MeCN as eluents. Fractions containing the desired compound were evaporated and further purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M ammonia in methanol and pure fractions were evaporated to dryness to afford 4-[[4-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperazin-1-yl]methyl]aniline (32 mg, 56%).

Workup

  1. customevaporated to dryness
  2. customThe crude product was purified by preparative HPLC
  3. additionFractions containing the desired compound
  4. customwere evaporated
  5. customfurther purified by ion exchange chromatography
  6. washThe desired product was eluted from the column
  7. customwere evaporated to dryness

Sources & evidence

ORD record
ord-515b3e422faf4792a5e48bd7f9ec9885
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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