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

HRID 1522637Notes

Reaction equation

HRID 1522637 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.[F:66][C:67]1[CH:72]=[CH:71][C:70]([F:73])=[CH:69][C:68]=1[C:74]1[CH:79]=[C:78]([NH2:80])[C:77]([CH3:81])=[CH:76][N:75]=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.CO.C(O[Pd]OC(=O)C)(=O)C>[F:66][C:67]1[CH:72]=[CH:71][C:70]([F:73])=[CH:69][C:68]=1[C:74]1[CH:79]=[C:78]([NH:80][C:48]2[CH:53]=[CH:52][N:51]=[C:50]3[CH:49]=[N:56][N:55]([CH2:57][C:58]4[CH:59]=[CH:60][C:61]([O:64][CH3:65])=[CH:62][CH:63]=4)[C:54]=23)[C:77]([CH3:81])=[CH:76][N:75]=1.[F:66][C:67]1[CH:72]=[CH:71][C:70]([F:73])=[CH:69][C:68]=1[C:74]1[CH:79]=[C:78]([NH:80][C:48]2[C:49]3[C:50](=[CH:54][N:55]([CH2:57][C:58]4[CH:63]=[CH:62][C:61]([O:64][CH3:65])=[CH:60][CH:59]=4)[N:56]=3)[N:51]=[CH:52][CH:53]=2)[C:77]([CH3:81])=[CH:76][N:75]=1

Participants

9

Reactant 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 674695617-Iodo-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridineHCID 674696792-(2,5-Difluorophenyl)-5-methylpyridin-4-amine

Product 2

HCID 67469557N-(2-(2,5-difluorophenyl)-5-methylpyridin-4-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridin-7-amineHCID 67470417N-(2-(2,5-difluorophenyl)-5-methylpyridin-4-yl)-1-(4-methoxybenzyl)-1H-pyrazolo[4,3-b]pyridin-7-amine

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
40 °C

Procedure

(R)-BINAP (1.396 g, 2.243 mmol), diacetoxypalladium (0.117 g, 0.520 mmol) and toluene (15 mL) were combined and stirred at 40° C. for 10 minutes. 7-Iodo-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridine (1.9 g, 5.20 mmol) suspended in toluene (20 mL), 2-(2,5-difluorophenyl)-5-methylpyridin-4-amine (1.146 g, 5.20 mmol) and sodium 2-methylpropan-2-olate (0.750 g, 7.80 mmol) were added and the mixture was heated at 100° C. overnight. The reaction mixture was then cooled, diluted with MeOH (10 mL) and absorbed directly onto silica and purified by column chromatography (NH silica column), eluted with EtOAc/hexanes (50-100%) to give N-(2-(2,5-difluorophenyl)-5-methylpyridin-4-yl)-1-(4-methoxybenzyl)-1H-pyrazolo[4,3-b]pyridin-7-amine and N-(2-(2,5-difluorophenyl)-5-methylpyridin-4-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridin-7-amine.

Workup

  1. temperaturethe mixture was heated at 100° C. overnight
  2. temperatureThe reaction mixture was then cooled
  3. customabsorbed directly onto silica
  4. custompurified by column chromatography (NH silica column)
  5. washeluted with EtOAc/hexanes (50-100%)

Sources & evidence

ORD record
ord-a5ea55368b424b2dad8588f890013f89
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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