Trifluoroacetic acid → HCID 60142832, compound

HRID 1475940Notes

Reaction equation

HRID 1475940 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:29](/[CH:30]=[CH:31]/[CH2:32][N:33]3[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]3)=[C:11]3[CH:12]=[C:13]([C:16]([N:18]([CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27])[CH2:19][CH2:20][CH:21]([CH3:23])[CH3:22])=[O:17])[CH:14]=[CH:15][N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:29]([CH2:30][CH2:31][CH2:32][N:33]3[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]3)=[C:11]3[CH:12]=[C:13]([C:16]([N:18]([CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27])[CH2:19][CH2:20][CH:21]([CH3:23])[CH3:22])=[O:17])[CH:14]=[CH:15][N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 12052Triethylsilane2×HCID 516892Sodium BicarbonateHCID 60142700HCID 60142700, compound

Product 1

HCID 60142832HCID 60142832, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

In a 15 mL sealed tube were added compound of Example 72i.e. (E)-2-(3-chlorophenyl)-N,N-diisopentyl-3-(3-(piperidin-1-yl)prop-1-en-1-yl)pyrazolo[1,5-a]pyridine-5-carboxamide (160 mg, 0.299 mmol), trifluoroacetic acid (0.069 ml, 0.896 mmol), and triethylsilane (0.143 ml, 0.896 mmol) in chloroform (5 ml) and the mixture was heated to 80-100° C. overnight, cooled down to room temperature and assayed for conversion by HPLC/LCMS. LC indicated homogenous peak but LCMS indicated the presence of both olefin and saturated compounds. Then 140 μL of TFA and 280 μL of triethylsilane were added and the mixture was heated to 100° C. for 5 days and cool down to room temperature. Saturated sodium bicarbonate was slowly added and the separated organic layer was washed with brine and dried over sodium sulfate, filtered and evaporated under reduced pressure. The crude material was dissolved in DMF and purified on a reverse-phase Zorbax SB-C18 column 21.2×100 mm and was eluted with MeOH-water-0.1% TFA. Isocratic 30% for 3 minutes then Gradient: 30% to 100% MeOH over 14 minutes. LCMS m/z 537.3 (M+H)+, ret. time=2.55 min.

Workup

  1. customIn a 15 mL sealed tube
  2. temperaturethe mixture was heated to 100° C. for 5 days
  3. temperaturecool down to room temperature
  4. washthe separated organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. dissolutionThe crude material was dissolved in DMF
  9. custompurified on a reverse-phase Zorbax
  10. washcolumn 21.2×100 mm and was eluted with MeOH-water-0.1% TFA
  11. waitGradient: 30% to 100% MeOH over 14 minutes

Sources & evidence

ORD record
ord-0f3d88cd803c4493affb2aa2af8f87c3
Source dataset
uspto-grants-2015_04
Patent number
US09018395B2

Reaction notes

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