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

HRID 1522582Notes

Reaction equation

HRID 1522582 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

Participants

7

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 1

HCID 54671159N-(2-(5-chloro-2-fluorophenyl)pyridin-4-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridin-7-amineYield 36.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
40 °C

Procedure

Into a 5 mL oven-dried microwave vial was added (R)-BINAP (159 mg, 0.255 mmol) and diacetoxypalladium (13.28 mg, 0.059 mmol). Toluene (2 mL) was added and the solution was stirred at 40° C. for 10 min. Then 7-iodo-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridine (216 mg, 0.592 mmol) in 2 mL of toluene was added, followed by 2-(5-chloro-2-fluorophenyl)pyridin-4-amine (132 mg, 0.592 mmol) and sodium 2-methylpropan-2-olate (85 mg, 0.887 mmol). Nitrogen was sparged into the solution for about 2 minutes, and the reaction was heated in a 100° C. oil bath over night. The reaction mixture was cooled and purified using silica column chromatography (0-5 methanol/dichloromethane) to give a residue. The residue was further purified by silica column chromatography (1:1 Ethyl acetate/hexanes) gave 100 mg of N-(2-(5-chloro-2-fluorophenyl)pyridin-4-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridin-7-amine. MS [M+H] found 460.3.

Workup

  1. customInto a 5 mL oven-dried microwave vial
  2. customNitrogen was sparged into the solution for about 2 minutes
  3. temperaturethe reaction was heated in a 100° C. oil bath over night
  4. temperatureThe reaction mixture was cooled
  5. custompurified
  6. customto give a residue
  7. customThe residue was further purified by silica column chromatography (1:1 Ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-3d37e529e0df45a6aa1243acbc9fe46a
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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