Trifluoroacetic acid → (R)-3-(6-(3-phenylpiperazin-1-yl)-3-(trifluoromethyl)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine

HRID 717587Notes

Reaction equation

HRID 717587 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[N:10](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:9]=2)[CH:5]=[CH:4][CH:3]=1.[C:36]1([C@H:42]2[CH2:47][NH:46][CH2:45][CH2:44][NH:43]2)[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2C)CCCCC1.C([SiH](CC)CC)C.C(O)([C:89]([F:92])([F:91])[F:90])=O>COCCOC.C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:36]1([C@H:42]2[NH:43][CH2:44][CH2:45][N:46]([C:2]3[N:7]=[C:6]([C:8]4[C:16]5[C:11](=[N:12][CH:13]=[CH:14][CH:15]=5)[NH:10][N:9]=4)[C:5]([C:89]([F:92])([F:91])[F:90])=[CH:4][CH:3]=3)[CH2:47]2)[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

10

Reactant 6

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 1514412HCID 1514412, compoundHCID 27349382-(Dicyclohexylphosphino)-2'-methylbiphenylHCID 23676156Sodium t-butoxideHCID 866659333-(6-bromopyridin-2-yl)-1-trityl-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 178506203(R)-3-(6-(3-phenylpiperazin-1-yl)-3-(trifluoromethyl)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridineYield 29%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 3-(6-bromo-2-pyridyl)-1-trityl-pyrazolo[5,4-b]pyridine (100 mg, 0.1933 mmol) and (2S)-2-phenylpiperazine (54.56 mg, 0.2320 mmol) in DME (2.500 mL) was treated with sodium t-butoxide (27.87 mg, 0.2900 mmol) followed by dicyclohexyl-[2-(o-tolyl)phenyl]phosphane (7.046 mg, 0.01933 mmol) and Palladium acetate (4.340 mg, 0.01933 mmol). The mixture was allowed to stir at 95 degrees in a sealed tube overnight. The mixture was allowed to cool, filtered through celite and concentrated to give a yellow oil. This was taken up in DCM (6 ml) and cooled to 0° C. Triethylsilane (0.12 mL) and TFA (1 mL) were added and the reaction stirred at 0° C. for 1 hour. The solvent was removed in vacuo and the residue purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100 A 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 (20 mg, 29% Yield).

Workup

  1. temperatureto cool
  2. filtrationfiltered through celite and
  3. concentrationconcentrated
  4. customto give a yellow oil
  5. stirringthe reaction stirred at 0° C. for 1 hour
  6. customThe solvent was removed in vacuo
  7. customthe residue purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100 A column, gradient 10%-95% B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25 mL/min]
  8. customThe fractions were collected
  9. customfreeze-dried

Sources & evidence

ORD record
ord-bca3a07d061043419da7e83b79ecc88d
Source dataset
uspto-grants-2015_11
Patent number
US09193722B2

Reaction notes

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