Hexachloroethane → 3-(8-Aza-bicyclo[3.2.1]oct-8-yl)-6-fluoro-[1,2,4]triazolo[4,3-a]pyridine
Reaction equation
ClC(Cl)(Cl)C(Cl)(Cl)Cl.[F:9][C:10]1[CH:11]=[CH:12][C:13]([NH:16][NH:17][C:18]([N:20]2[CH:25]3[CH2:26][CH2:27][CH:21]2[CH2:22][CH2:23][CH2:24]3)=O)=[N:14][CH:15]=1.C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[CH:25]12[N:20]([C:18]3[N:14]4[CH:15]=[C:10]([F:9])[CH:11]=[CH:12][C:13]4=[N:16][N:17]=3)[CH:21]([CH2:27][CH2:26]1)[CH2:22][CH2:23][CH2:24]2Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 60 °C
Procedure
Hexachloroethane (296 mg, 1.25 mmol) was added portionwise over 5 min at RT to a stirred mixture of Intermediate 122b (165 mg, 0.62 mmol), triethylamine (350 μL, 2.50 mmol) and triphenylphosphine (327 mg, 1.25 mmol) in THF (10 mL). The reaction mixture was stirred for 3.5 h and then heated to 60° C. overnight. The temperature was increased to 70° C. for 5 days, then cooled and concentrated in vacuo. The residue was taken up in dioxane, and re-treated with hexachloroethane (150 mg, 0.63 mmol) and triethylamine (200 μL, 1.43 mmol) at 115° C. overnight. The mixture was cooled and concentrated in vacuo. The residue was taken up in methanol and loaded onto an SCX cartridge. The cartridge was washed with MeOH and the product eluted with 2M NH3 in MeOH and concentrated in vacuo to give the title compound (117 mg, 76%). LCMS (Method 3): Rt 2.88 min, m/z 247 [MH+].
Workup
- temperatureThe temperature was increased to 70° C. for 5 days
- temperaturecooled
- concentrationconcentrated in vacuo
- temperatureThe mixture was cooled
- concentrationconcentrated in vacuo
- washThe cartridge was washed with MeOH
- washthe product eluted with 2M NH3 in MeOH
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-88a19b1f64db4512ae6e77e96fc7ba8c
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09315503B2
Reaction notes
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