Binap, (A+-)- → N-(2-(5-chloro-2-fluorophenyl)pyridin-4-yl)-1-(4-methoxybenzyl)-1H-pyrazolo[4,3-b]pyridin-7-amine

HRID 1522584Notes

Reaction equation

HRID 1522584 reaction equation
C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.I[C:48]1[C:49]2[C:50](=[CH:54][N:55]([CH2:57][C:58]3[CH:63]=[CH:62][C:61]([O:64][CH3:65])=[CH:60][CH:59]=3)[N:56]=2)[N:51]=[CH:52][CH:53]=1.[Cl:66][C:67]1[CH:68]=[CH:69][C:70]([F:80])=[C:71]([C:73]2[CH:78]=[C:77]([NH2:79])[CH:76]=[CH:75][N:74]=2)[CH:72]=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.C(O[Pd]OC(=O)C)(=O)C>[Cl:66][C:67]1[CH:68]=[CH:69][C:70]([F:80])=[C:71]([C:73]2[CH:78]=[C:77]([NH:79][C:48]3[C:49]4[C:50](=[CH:54][N:55]([CH2:57][C:58]5[CH:63]=[CH:62][C:61]([O:64][CH3:65])=[CH:60][CH:59]=5)[N:56]=4)[N:51]=[CH:52][CH:53]=3)[CH:76]=[CH:75][N:74]=2)[CH:72]=1.[Cl:66][C:67]1[CH:68]=[CH:69][C:70]([F:80])=[C:71]([C:73]2[CH:78]=[C:77]([NH:79][C:48]3[CH:53]=[CH:52][N:51]=[C:50]4[CH:49]=[N:56][N:55]([CH2:57][C:58]5[CH:59]=[CH:60][C:61]([O:64][CH3:65])=[CH:62][CH:63]=5)[C:54]=34)[CH:76]=[CH:75][N:74]=2)[CH:72]=1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 674695617-Iodo-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridineHCID 674696072-(5-Chloro-2-fluorophenyl)pyridin-4-amine

Product 2

HCID 54671158N-(2-(5-chloro-2-fluorophenyl)pyridin-4-yl)-1-(4-methoxybenzyl)-1H-pyrazolo[4,3-b]pyridin-7-amineHCID 54671159N-(2-(5-chloro-2-fluorophenyl)pyridin-4-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridin-7-amine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
40 °C

Procedure

(R)-BINAP (0.808 g, 1.298 mmol), diacetoxypalladium (0.068 g, 0.301 mmol) and Toluene (10 mL) was added to a round bottom flask and the solution was stirred at 40° C. for 10 minutes. This mixture was removed from heat and a suspension of 7-iodo-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridine (1.1 g, 3.01 mmol), 2-(5-chloro-2-fluorophenyl)pyridin-4-amine (0.671 g, 3.01 mmol) and sodium 2-methylpropan-2-olate (0.434 g, 4.52 mmol) in toluene (11 mL) was added. The reaction mixture was sparged with nitrogen and heated at 100° C. overnight. The reaction mixture was cooled to room temperature, concentrated in-vacuo and purified on a silica gel column chromatography (Ethyl acetate/hexanes 1:1) to give as a mixture N-(2-(5-chloro-2-fluorophenyl)pyridin-4-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridin-7-amine and N-(2-(5-chloro-2-fluorophenyl)pyridin-4-yl)-1-(4-methoxybenzyl)-1H-pyrazolo[4,3-b]pyridin-7-amine as a yellow foam; MS [M+H] found 460.3.

Workup

  1. customThis mixture was removed
  2. temperaturefrom heat
  3. additionwas added
  4. customThe reaction mixture was sparged with nitrogen
  5. temperatureheated at 100° C. overnight
  6. temperatureThe reaction mixture was cooled to room temperature
  7. concentrationconcentrated in-vacuo
  8. custompurified on a silica gel column chromatography (Ethyl acetate/hexanes 1:1)

Sources & evidence

ORD record
ord-d344abbfa75f486d84f949e3a3ee22c1
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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