Potassium Carbonate → (S)-3-(6-(3-isobutylpiperazin-1-yl)-3-(trifluoromethyl)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine

HRID 1046567Notes

Reaction equation

HRID 1046567 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[NH:10][N:9]=2)[C:5]([C:17]([F:20])([F:19])[F:18])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].C([N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH:35]1[CH2:40][CH:41]([CH3:43])[CH3:42])(OC(C)(C)C)=O>CN(C=O)C.CCOC(C)=O.C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH2:40]([C@@H:35]1[NH:34][CH2:39][CH2:38][N:37]([C:2]2[N:7]=[C:6]([C:8]3[C:16]4[C:11](=[N:12][CH:13]=[CH:14][CH:15]=4)[NH:10][N:9]=3)[C:5]([C:17]([F:20])([F:19])[F:18])=[CH:4][CH:3]=2)[CH2:36]1)[CH:41]([CH3:43])[CH3:42]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 45073240Tert-butyl 2-isobutylpiperazine-1-carboxylateHCID 1785061723-(6-chloro-3-(trifluoromethyl)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 178445826(S)-3-(6-(3-isobutylpiperazin-1-yl)-3-(trifluoromethyl)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridineYield 57.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 3-(6-chloro-3-(trifluoromethyl)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine (50 mg, 0.1674 mmol), K2CO3 (46.27 mg, 0.3348 mmol) and N-BOC isobutyl piperazine (81.14 mg, 0.3348 mmol) in DMF (1.786 mL) were heated at 90° C. for 100 mins in the microwave. The reaction was worked up by diluting with EtOAc, washing with bicarb and brine. This was dried over MgSO4, filtered and evaporated to dryness to give an orange residue. The residue was taken up in TFA/DCM (1 ml/3 ml) and stirred at RT for 2 hours. Reaction mixture was concentrated and the resultant residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100A column, gradient 10%-95% B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound as a white solid (39 mg, 36% Yield).

Workup

  1. washwashing with bicarb and brine
  2. dry with materialThis was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customto give an orange residue
  6. customReaction mixture
  7. concentrationwas concentrated
  8. customthe resultant residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100A column, gradient 10%-95% B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25 mL/min]
  9. customThe fractions were collected
  10. customfreeze-dried

Sources & evidence

ORD record
ord-b8c854c4aa7049c8a17e09afa8e32af2
Source dataset
uspto-grants-2013_10
Patent number
US08569337B2

Reaction notes

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