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

HRID 1522569Notes

Reaction equation

HRID 1522569 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:81])=[C:71]([C:73]2[N:78]=[C:77]([NH2:79])[C:76]([CH3:80])=[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:81])=[C:71]([C:73]2[N: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)[C:76]([CH3:80])=[CH:75][N:74]=2)[CH:72]=1.[Cl:66][C:67]1[CH:68]=[CH:69][C:70]([F:81])=[C:71]([C:73]2[N: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)[C:76]([CH3:80])=[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 674696142-(5-Chloro-2-fluorophenyl)-5-methylpyrimidin-4-amine

Product 2

HCID 67469566N-(2-(5-chloro-2-fluorophenyl)-5-methylpyrimidin-4-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridin-7-amineHCID 67470498N-(2-(5-chloro-2-fluorophenyl)-5-methylpyrimidin-4-yl)-1-(4-methoxybenzyl)-1H-pyrazolo[4,3-b]pyridin-7-amine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
40 °C

Procedure

(R)-BINAP (1.102 g, 1.770 mmol), diacetoxypalladium (0.092 g, 0.411 mmol) and toluene (30 mL) were combined and stirred at 40° C. for 10 minutes. 7-Iodo-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridine (1.500 g, 4.11 mmol) suspended in toluene (8 mL), 2-(5-chloro-2-fluorophenyl)-5-methylpyrimidin-4-amine (0.976 g, 4.11 mmol) and sodium 2-methylpropan-2-olate (0.592 g, 6.16 mmol) were added. The mixture was sparged with nitrogen and heated at 100° C. overnight. The reaction was then cooled, MeOH (5 mL) was added and the mixture was concentrated directly onto silica gel and purified by chromatography eluted with EtOAc/hexanes step gradient (35-50%) to give N-(2-(5-chloro-2-fluorophenyl)-5-methylpyrimidin-4-yl)-1-(4-methoxybenzyl)-1H-pyrazolo[4,3-b]pyridin-7-amine and N-(2-(5-chloro-2-fluorophenyl)-5-methylpyrimidin-4-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridin-7-amine. ESI-MS: m/z 475.3 (M+H).

Workup

  1. customThe mixture was sparged with nitrogen
  2. temperatureheated at 100° C. overnight
  3. temperatureThe reaction was then cooled
  4. additionMeOH (5 mL) was added
  5. concentrationthe mixture was concentrated directly onto silica gel
  6. custompurified by chromatography
  7. washeluted with EtOAc/hexanes step gradient (35-50%)

Sources & evidence

ORD record
ord-7e3ad5b4d48f43e29c016028482b30bc
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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